Power addition operation logic circuit construction method based on DNA domain coding
Through the DNA domain coding strategy, the problem of NC instability of logic circuits in dual-track strategy design was solved, and the power addition operation logic circuit was constructed, which achieved faster reaction speed and better parallelism, simplified circuit construction, and solved the problem of large-scale The stability and complexity challenges of scale logic circuits.
Patent Information
- Application Number
- CN202411130879.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-08-16
- Publication Date
- 2024-12-10
- Estimated Expiration
- Not applicable · inactive patent
AI Technical Summary
Logic circuits designed based on dual-track strategy encounter NATO instability problems when implementing large-scale complex logic operations, resulting in an increase in the number of DNA strands and an increase in experimental difficulty, which limits the development of large-scale molecular logic circuits.
Adopt the DNA domain encoding strategy, by encoding the domain of the DNA strand, use a coding strategy with better stability, avoid using high and low concentrations to represent logic values, build domain encoding fan doors, amplifiers and fluorescence report gates, and realize power addition operation logic circuits , use DSD simulation software to verify its correctness.
The error output problem caused by NATO gate was successfully solved, the reaction speed and parallelism were improved, the circuit construction was simplified, the reaction time was reduced, and the potential in large-scale complex logic circuits was demonstrated.
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Figure CN119106716A_ABST
Abstract
Description
Technical Field
[0001] The present invention relates to the field of biological computing technology, and in particular to a method for constructing a power addition operation logic circuit based on DNA domain coding. Background Art
[0002] DNA chain displacement technology is a widely used computing model in the field of biological computing in recent years. Due to its simple operation, self-initiation, sensitivity and accuracy, it has been promoted and applied to the construction of large-scale molecular logic circuits. At present, digital logic circuits designed based on the dual-track strategy are developing rapidly. However, with the deepening of research, it is found that more and more complex large-scale logic circuits need to be realized, but the essence of the dual-track circuit is to exchange the complexity of the circuit for the stability of the circuit. The number of gate circuits it requires is huge. The larger and more complex the circuit scale is, the more DNA chains are required, which increases the difficulty of the experiment and even makes it difficult to achieve. In the long run, the method of designing logic circuits based on the dual-track strategy limits the development of large-scale molecular logic circuits.
[0003] Based on this problem, it becomes an urgent problem to fundamentally solve the instability problem of NOT gate caused by concentration and further construct the domain-coded logic operation module to realize the operation function of logic AND or NOT. Summary of the invention
[0004] In view of the shortcomings of the prior art, the present invention provides a method for constructing a power addition operation logic circuit based on DNA domain coding. The power addition operation molecular circuit is designed by using DNA chain replacement technology, adopting a domain coding strategy, and combining an input mapping module. This design uses a domain coding strategy with better stability on the premise of utilizing hybridization pairing between DNA molecules, avoids using high and low concentrations to represent the high and low logic values, encodes the domain of the DNA signal chain, and uses coding "1" and coding "0" to distinguish the positive and negative logic values of the DNA chain, successfully solving the problem of erroneous output caused by the NOT gate.
[0005] To achieve the above objectives, the present invention is implemented through the following technical solutions: A method for constructing a power addition operation logic circuit based on DNA domain coding, comprising the following steps:
[0006] Step 1: Based on the DNA chain structure, a domain coding strategy is proposed to encode the special domains of the DNA chain, instead of using the high and low concentrations of the DNA chain to represent positive and negative logic values;
[0007] Step 2: Use domain coding strategy to construct domain coding fan-out gates, domain coding amplifiers, and fluorescence reporter gates;
[0008] Step 3: construct a domain coding logic operation module, such as a one-input one-output logic operation module, a two-input one-output logic operation module, a three-input one-output logic operation module, and an N-input one-output logic operation module;
[0009] Step 4: Use the domain coded logic operation module to build a DNA circuit for calculating the four-digit square root. Use the DSD simulation software to verify its correctness and make a comparative analysis with the four-digit square root circuit built with two tracks.
[0010] Step 5: Use the domain coded logic operation module to build a DNA circuit for power addition operation, verify its correctness with the DSD simulation software, and make a comparative analysis with the power addition DNA operation circuit built with dual tracks.
[0011] Preferably, the domain coding strategy in step 1 is to divide the DNA signal chain centered on the toehold T into two parts, the left part can be complementary paired with the same domain structure of the upstream signal chain, and the right part determines the logic value of each single chain; according to the different domain codes, the DNA single chain can encode the domain into four codes: (0, 0), (0, 1), (1, 0), (1, 1), code 0 corresponds to the logic value "0", code 1 represents the logic value "1", if the right side code is "0", it represents that the logic value of the DNA chain is negative, if the right side code is "1", it represents that the logic value of the DNA chain is positive. The domain coding structure of the DNA chain is designed as: A0()=<a^0b^T^c^0d^> ,A1()=<a^0b^T^c^1d^> ,A2()=<a^1b^T^c^0d^> ,A3()=<a^1b^T^c^1d^> Among them, T^ is the small branch domain, and <> represents the upper chain structure part of the DNA chain.
[0012] Preferably, the fan-out gate constructed using the domain coding strategy in step 2 is composed of four double chains (labeled as F01, F02, F03, F04) and two fuel chains (H0, H1), and the double chain structure is designed as: F01()={T^*}[a^0b^T^]<e^0f^> , F02()={T^*}[a^1b^T^]<e^1f^> , F03()={T^*}[a^0b^T^]<g^0k^> , F04()={T^*}[a^1b^T^]<g^1k^> , the fuel chain structure is designed as: H0()=<a^0b^T^hL^h hR^> ,H1()=<a^1b^T^hL^hhR^> ;
[0013] Wherein, T^ is a small branch point domain, <> represents the upper chain structure part of the DNA chain, [] represents the double-stranded structure part of the DNA chain that has been complementary paired, : represents the double-stranded structure domain used to connect two parts, {} represents the lower chain structure part of the DNA chain, ^ is used to mark the upper chain domain, and ^* is used to mark the lower chain domain;
[0014] The reaction equation of domain coding 2-fan-out door is as follows:
[0015] A0+F01→sp8+output1(1)
[0016] A0+F02→sp8+output2(2)
[0017] A0+F03→sp10(3)
[0018] A0+F04→sp9(4)
[0019] H0+sp8→sp7+A0(5)
[0020] Reaction equations (1)-(4) are the reaction process between the input strand A0 and the domain-encoded fan-out double strands F01-F04. A0 and F01-F04 on the left side of the arrow are the reactants, and the new product is on the right side of the arrow. The forward reaction rate and reverse unbinding rate of DNA strand displacement are set to 3.0e-4nM, respectively. -1 s -1 and 0.1126s -1 , the subsequent reaction processes are all at this reaction rate. Reaction equation (5) is the reaction process between the fuel chain H0 and the waste sp8. The input chain A0 is regenerated on the right side of the arrow. At this time, the concentration of the A0 input chain can be set equal to the concentration of the double chain of the fan-outlet. The double chains of all fan-outlets are set equal. In order to make the concentration of the output chain higher, the concentration of the fuel chain is set to twice the sum of the concentrations of the double chains of all fan-outlets.
[0021] The domain coding amplifier in step 2 is composed of two double chains Amp0 and Amp1, and two fuel chains H0 and H1. The Amp0 double chain is designed as {T^*}[a1^0a2^T^]<c1^0c2^> , combined with H0 to complete the task of amplifying logic 0, the Amp1 double chain design is {T^*}[a1^1a2^T^]<c1^1c2^> , combined with H1 to complete the task of amplifying logic 1.
[0022] The reaction equation of the domain coding amplifier is as follows:
[0023] A0+Amp0→sp10+out(6)
[0024] A0+Amp1→sp11(7)
[0025] H0+sp10→sp6+A0(8)
[0026] H1+sp10→sp7(9)
[0027] Reaction equations (6)-(7) are the reaction process between the input chain A0 representing the logic value "0" and the double chain of the domain coding amplifier. Here, the input chain concentration is set to 1x (1x = 10 3 nM), the amplifier double-chain concentration is set to 1x, the fuel chain concentration is set to twice the double-chain concentration, the input chain A0 undergoes chain displacement reaction with the double-chains Amp1 and Amp2 at the same time through the middle foothold T, and only the single-chain out is formed on the reaction path with Amp0, while Amp1 only produces the intermediate product sp11, and no single-chain is produced; at this time, the logic value of the single-chain out remains the same as the logic value of the input chain A0, both representing the logic value "0", but its concentration is raised to 1x concentration again.
[0028] If the input logic value is "1" for the signal chain A1, the input chain A1 undergoes chain displacement reaction with the double chains Amp0 and Amp1 at the same time through the middle foothold T, and only a single chain is formed on the reaction path with Amp1, while Amp0 only produces an intermediate product, and no single chain is produced; the output single chain logic value remains the same as the logic value of the input chain A1, both representing the logic value "1", and the concentration is raised to 1x concentration again. Reaction equations (8)-(9) are the process in which the fuel chains H0 and H1 undergo chain displacement with the intermediate product chain sp10 at the same time, and the input chain A0 is regenerated after displacement with H0;
[0029] The fluorescent reporter gate in step 2 is used to convert the output signal chain into a fluorescent signal that is easy to detect. The domain-coded fluorescent reporter gate is composed of two double-chains Rep0 and Rep1. The single-chain part on the right side of the double-chain is a fluorescent detection domain with a fluorescent quenching group. The output logic value can be known by detecting the coding domain on the fluorophore, and the output chain result can be converted into a fluorescent signal of different colors;
[0030] The reaction equation for the domain-encoded fluorescent reporter gate is shown below:
[0031] Out+Rep0→sp6+rep(10)
[0032] Out+Rep1→sp5(11)
[0033] Reaction (10) is the reaction process between the output chain Out and the fluorescent reporter chain Rep0. After the output chain reacts with the reporter chain, the intermediate products sp6 and rep on the right are generated. Rep is a fluorescent output chain with a fluorophore. The coding domain of the fluorescent chain can be detected to obtain the logical value. Reaction (11) is the reaction process between the output chain Out and the fluorescent reporter chain Rep1. The intermediate product sp5 is obtained on the right side of the reaction, but no fluorescent signal chain falls off.
[0034] Preferably, the domain encoding logic operation module in step 3 is divided into: a one-input one-output logic operation module, a two-input one-output logic operation module, a three-input one-output logic operation module and an N-input one-output logic operation module according to the number of input terminals. The main basis of these operation modules is obtained according to the mapping relationship in mathematics. The number of DNA double strands and the length of the double-stranded domain contained in the operation module are determined according to the number of input terminals, and the logic function is determined by programming the logic value of the double-stranded domain.
[0035] The one-input one-output logic operation module is composed of two DNA double strands, and the DNA double strands are designed as {T^*}[a^0b^T^]<e^k1f^> and {T^*}[a^1b^T^]<e^k2f^> , k1 and k2 on the single-stranded domain are encoded by 2 2 =4 encoding situations, when k1, k2 are (0,0), the reset function is realized; when k1, k2 are (0,1), the YES gate function is realized; when k1, k2 are (1,0), the NOT gate function is realized; when k1, k2 are (1,1), the reset function is realized, and the reaction process of the NOT gate of the one-input and one-output logic operation module is as follows:
[0036] A0+F01→sp5+output(12)
[0037] A0+F02→sp6(13)
[0038] Reaction equations (12)-(13) use an input logic operation module to realize the reaction of inverting the logic value of input chain A0. The right coding domain of input chain A0 takes the value 0, representing the logic value "0". After entering the reaction pool, it hybridizes and pairs with double-stranded chains F01 and F02 at the same time. After A0 is paired with F01, a single-stranded output and waste sp5 are generated. The logic value of the detached single-stranded output is exactly opposite to the logic value of the input chain A0, realizing the NOT gate function. After pairing with F02, no single-strand is detached, and only a double-stranded sp6 is generated.
[0039] The two-input one-output logic operation module consists of 2 2= 4 DNA double strands, DNA double strands are designed as F01 = {T^*}[a^0b^T^c^0d^]<e^k1f^> 、F02={T^*}[a^0b^T^c^1d^]<e^k2f^> , F03 = {T^*}[a^1b^T^c^0d^]<e^k3f^> , F04 = {T^*}[a^1b^T^c^1d^]<e^k4f^> , k1, k2, k3, k4 on the single-chain domain can encode 2 4 =16 cases. When k1, k2, k3, k4 are (0, 0, 0, 0), the reset function is realized; when k1, k2, k3, k4 are (0, 0, 0, 1), the AND function is realized; when k1, k2, k3, k4 are (1, 1, 1, 0), the AND function can be realized; when k1, k2, k3, k4 are (0, 1, 1, 1), the OR function is realized; when k1, k2, k3, k4 are (1, 0, 0, 0), the OR function is realized; when k1, k2, k3, k4 are (0, 1, 1, 0), the XOR function is realized; when k1, k2, k3, k4 are (1, 0, 0, 1), the XOR function is realized; when k1, k2, k3, k4 are (1, 1, 1, 1), the reset function is realized. The reaction process of the two-input one-output logic operation module or gate is as follows:
[0040] A0+F01→sp27 (14)
[0041] A0+F02→sp26 (15)
[0042] A0+F03→sp25→sp23+waste1 (16)
[0043] A0+F04→sp24→sp21+waste1 (17)
[0044] A1+sp23→sp20 (18)
[0045] A1+sp21→sp19→sp17+sp18 (19)
[0046] sp17+amp1→sp14+sp15 (20)
[0047] sp14+Report→rep+waste2 (21)
[0048] The specific steps of the reaction process of the reaction formula are as follows: A0 and A1 are two input signal chains, representing logic value 0 and logic value 1 respectively. Input chain A0 first reacts with four double chains F01-F04 simultaneously to generate hybrid double chains sp27, sp26, sp25, and sp24 respectively, and the double-chain structures of sp25 and sp24 continue to be replaced by sp23, sp21 and an identical waste waste1. At this time, input chain A1 begins to undergo chain replacement reaction with sp23 and sp21 to generate hybrid double chains sp20 and sp19, and sp19 continues to split into single chains sp17 and sp18. Sp17 is used as an output chain to react with the amplifier gate double chain amp1 to generate single chain sp14 and double chain sp15. Sp14 reacts with the fluorescent reporter gate to output the final fluorescent signal chain rep. The logical value of this fluorescent signal chain is 1, which meets the logical function of the OR gate.
[0049] The input-output logic operation module is composed of 2 3 = 8 DNA double strands, DNA double strands are designed as F01 = {T^*}[a^0b^T^c^0d^T^e^0f^]<g^k1k^> , F02={T^*}[a^0b^T^c^0d^T^e^1f^]<g^k2k^> , F03={T^*}[a^0b^T^c^1d^T^e^0f^]<g^k3k^> , F04={T^*}[a^0b^T^c^1d^T^e^1f^]<g^k4k^> , F05={T^*}[a^1b^T^c^0d^T^e^0f^]<g^k5k^> , F06={T^*}[a^1b^T^c^0d^T^e^1f^]<g^k6k^> , F07={T^*}[a^1b^T^c^1d^T^e^0f^]<g^k7k^> , F08={T^*}[a^1b^T^c^1d^T^e^1f^]<g^k8k^> , k1, k2, k3, k4, k5, k6, k7, k8 on the single-chain domain can be encoded as 2 8 =256 cases, when k1, k2, k3, k4 are (0, 1, 1, 1, 1, 1, 0), the XOR function is realized; when k1, k2, k3, k4 are (0, 1, 1, 0, 1, 0, 0, 1), the full adder summation (full subtractor difference) function is realized;
[0050] Based on the above method for constructing a logic operation module, any n-input-one-output logic operation module can be constructed according to circuit requirements.
[0051] Preferably, in the step 4, a DNA circuit for obtaining a four-digit square root is constructed using a domain coding logic operation module, and four typical input values 0, 1, 4, and 9 are calculated. The DNA circuit for obtaining a four-digit square root constructed by the domain coding logic operation module consists of 4 logic NOT gates, 3 three-input logic AND gates, 1 two-input logic OR gate, and 1 two-input logic AND gate. Corresponding to the concept of the above-mentioned domain coding logic operation module, one-input, two-input, and three-input logic operation modules are used to implement it.
[0052] First, the input signals A0, A1, A2, and A3 are inverted through the logic NOT gate to obtain Then use 3 domain encoding fan-out gates to input chain A0, Perform fan-out operation to obtain signal chains with the same logic value. The encoding structures of input chains A0, A1, A2, and A3 are<i1L^b i1R^T^m1L^a m1R^> ,<i2L^b i2R^T^m2L^a m2R^> ,<i3L^b i3R^T^m3L^a m3R^> ,<i3L^b i3R^T^m4L^a m4R^> , all represent logical value 0. The specific reaction process of the 4 input chains being inverted through the logic NOT gate is as follows:
[0053] A0+NA0→sp94+sp91 (22)
[0054] A1+NA1→sp89+sp90 (23)
[0055] A2+NA2→sp87+sp88 (24)
[0056] A3+NA3→sp85+sp86 (25)
[0057] Reaction formulas (22)-(25) use a one-input one-output logic operation module to implement the reaction process of inverting the logic value of input chain A0. In reaction formula (22), after input chain A0 is paired with double-stranded NA0, single-stranded sp94 is generated, which is encoded as<m1L^am1R^T^u1L^b u1R^> and waste sp91, the logic value of the detached single-stranded sp94 is opposite to the logic value of the input chain A0, representing a logic value of 1; the reaction process of reaction formulas (23)-(25) is similar to reaction formula (22), and single-stranded sp89 is produced, which is encoded as<m2L^a m2R^T^u2L^b u2R^> , sp87 is encoded as<m3L^a m3R^T^u3L^b u3R^> and sp85 is encoded as<m4L^am4R^T^u4L^b u4R^> , which is opposite to the logic value of input chain A1, A2, and A3, and all represent logic value 1.
[0058] The fan-out operation is performed on the input chain A0 using three domain coded fan-out gates. The specific reaction process is as follows:
[0059] A0+I FA0→sp93+sp94(26)
[0060] A0+I FA1→sp92+sp94(27)
[0061] A1+NA1→sp89+sp90(28)
[0062] sp89+NFA10→sp82+sp83(29)
[0063] sp89+NFA11→sp81+sp83(30)
[0064] A2+NA2→sp87+sp88(31)
[0065] sp87+NFA20→sp79+sp80(32)
[0066] sp87+NFA21→sp78+sp80(33)
[0067] Reaction formulas (26)-(27) respectively fan out two single chains sp92 and sp93 with the same logic value as A0, both representing logic value 0; reaction formula (28) reverses the logic value of A1 single chain representing logic value 0 to obtain sp89 single chain representing logic value 1. In reaction formulas (29)-(30), sp89 single chain reacts with fan-out gate double chains NFA10 and NFA11 respectively, fanning out two single chains sp81 and sp82 with the same logic value. The structure of sp81 single chain is<u2L^b u2R^T^b2L^b b2R^> , representing a logical value of 1, and the single-chain structure of sp82 is<u2L^b u2R^T^b1L^b b1R^> , representing the logical value 1.
[0068] Reaction (31) inverts the logic value of the A2 single chain representing the logic value 0 to obtain the sp87 single chain representing the logic value 1. In reactions (32)-(33), the sp87 single chain reacts with the fan-out gate double chains NFA20 and NFA21 respectively, fanning out two single chains sp78 and sp79 with the same logic value. The structure of the sp78 single chain is<u3L^bu3R^T^b4L^bb4R^> , representing a logical value of 1, and the single-chain structure of sp82 is<u3L^bu3R^T^b3L^bb3R^> , representing the logical value 1.
[0069] Secondly, two three-input and one-output logic AND gate modules, one two-input logic OR gate and one two-input logic AND gate are used to implement AND operation and realize the logic value output of Y1. The specific reaction process of the two three-input and one-output logic AND gate modules is as follows:
[0070]
[0071] In reaction formula (34), after the input chain A2 and the inverted input chains A0 and A3 react with the double-stranded chain F6 of the three-input one-output module, the double-stranded structure of F6 is {T^*}[u4L^b u4R^T^]:[m3L^a m3R^T^]:[u1L^b u1R^T^]<c1L^a c1R^> , producing single-stranded sp60 and waste, the generated sp60 single-stranded<u1L^b u1R^T^c1L^a c1R^> ; In reaction formula (35), input chains A0, A3 and input chain After the double-stranded F11 of the three-input and one-output module reacts, single-stranded sp60 and waste are produced. The double-stranded structure of F11 is {T^*}[m4L^a m4R^T^]:[b3L^b b3R^T^]:[a1L^a a1R^T^]<c2L^a c2R^> The resulting sp64 single chain is<a1L^a a1R^T^c2L^a c2R^> .
[0072] The single-chain sp60 and sp64 obtained after the operation of the two logic and modules enter the two-input and one-output logic or gate module for logic or operation. The specific reaction process is as follows:
[0073] sp60+H1→sp55+waste(36)
[0074] sp64+sp55→sp49+waste(37)
[0075] H1 in reaction (36) is a double chain of two-input and one-output logic OR gates, and its encoding structure is {T^*}[c1L^ac1R^T^]:[c2L^a c2R^T^]<d1L^a d1R^> , with sp60 single chain<u1L^b u1R^T^c1L^a c1R^> After strand displacement, sp55 single strand is formed; in reaction equation (37), sp55 and sp64 single strand<a1L^a a1R^T^c2L^a c2R^> After strand displacement, a single-stranded sp49 is obtained, and the strand structure of sp49 is<c2L^a c2R^T^d1L^a d1R^> .
[0076] After the operation of the logic OR gate module, the generated single-chain sp49 and the single-chain sp82 of the input chain enter the two-input and one-output logic AND gate module for further AND operation. The specific reaction process is as follows:
[0077] sp49+H6→sp46+waste(38)
[0078] sp46+sp82→sp43+waste(39)
[0079] H6 in reaction (38) is a double chain of two-input and one-output logic AND gates, and its encoding structure is {T^*}[d1L^ad1R^T^]:[b1L^b b1R^T^]<d2L^a d2R^> , after reacting with single-stranded sp49, a double-stranded sp46 output and waste are obtained; in reaction formula (39), the double-stranded sp46 reacts with the single-stranded sp82 to produce a single-stranded sp43, and its encoding structure is<b1L^b b1R^T^d2L^a d2R^> .
[0080] The sp43 single chain obtained after the above logic operation reaction output is further amplified through the amplification gate. The specific amplification reaction process is as follows:
[0081] sp43+amp11→sp41+sp42(40)
[0082] In reaction formula (40), amp11 is a double chain of the amplification gate, and its structure is {T^*}[d2L^a d2R^T^]<pL^a pR^> After passing through the amplification gate, a single chain of sp41 and waste sp42 are generated. The single chain structure of sp41 is<d2L^a d2R^T^pL^a pR^> .
[0083] In order to more conveniently observe the output logic value, the single-chain sp41 is output in the form of a fluorescent chain, which is realized through the fluorescent reporting gate Report. The specific reaction process is as follows:
[0084] sp41+ReportL11→OUTL11+sp39(41)
[0085] ReportL11 in reaction formula (41) is the double chain of the fluorescent gate, and its structure is {T^*}[pL^a pR^] <fluor01>After passing through the fluorescent reporter gate, the single-stranded OUTL11 and the waste sp39 are generated. The single-stranded structure of OUTL11 is [pL^a pR^] <fluor01>, the output fluorescent chain logical value represents 0.
[0086] Finally, a three-input and one-output logic AND gate module is used to realize the logic value output of Y0. The reaction process is as follows:
[0087] sp78+B7→sp68+sp69(42)
[0088] sp69+sp81→sp63+sp62(43)
[0089] sp63+sp92→sp56+sp57(44)
[0090] In reaction formula (42), B7 is a domain-encoded double chain of a three-input and one-output AND gate, and its structure is {T^*}[b4L^bb4R^T^]:[b2L^b b2R^T^]:[a2L^a a2R^T^]<c3L^a c3R^> , after the sp78 single strand and the B7 double strand undergo strand displacement, a sp69 double strand mixture and waste sp68 are produced; in reaction formula (43), after the sp69 double strand mixture and the sp81 single strand undergo strand displacement, waste sp62 and a double strand mixture sp63 are produced; in reaction formula (44), after the double strand mixture sp63 and the sp92 single strand undergo strand displacement, a sp56 single strand and a sp57 double strand mixture are produced, wherein sp56 is the desired single strand output, and its strand structure is<a2L^a a2R^T^c3L^a c3R^> .
[0091] The single-stranded sp56 continues to be amplified through the amplification gate, and then output in the form of a fluorescent chain through the fluorescence reporter gate. The specific reaction process is as follows:
[0092] sp56+amp21→sp51+sp52(45)
[0093] sp51+ReportL21→sp47+OUTL21(46)
[0094] In reaction formula (45), amp21 is a double-stranded amplification gate, and its structure can be set as {T^*}[c3L^a c3R^T^]<zL^azR^> After chain displacement with single-stranded sp56, sp51 single-stranded and sp52 double-stranded wastes are generated. The chain structure of sp51 is<c3L^ac3R^T^zL^a zR^> In reaction equation (46), after the strand displacement between sp51 and the fluorescent reporter gate ReportL21, double-stranded waste sp47 and fluorescent chain OUTL21 are generated. The chain structure of OUTL21 is<zL^a zR^fluor11> .
[0095] Compared with the four-digit square root circuit designed with a dual-track circuit, when the initial parameters of the species are set to be consistent, the initial reactants of the four-digit square root circuit designed with domain coding are reduced from 130 to 61, and the reaction time is reduced to 1 / 24 of that of the dual-track circuit. The circuit construction is simpler and the output results are more stable.
[0096] Preferably, the method of the power addition molecular circuit in step five is: obtaining the truth table of the power addition operation logic circuit through logical relations, constructing the power addition logic circuit according to the truth table, and the power addition logic circuit is mainly composed of 4 NOT gates, 13 AND gates, and 5 OR gates.
[0097] The output expression of the power addition logic circuit is:
[0098]
[0099]
[0100] Y 4 =X 3 X 2 X 1 X 0
[0101] Preferably, in step 5, the domain coding logic operation module and the power addition logic circuit are used to construct a power addition molecular circuit to achieve 2 x with 2 x Addition operation (x is 0-3), for example 2 0 with 2 3 The addition operation.
[0102] The power addition numerator operation circuit is composed of 4 NOT gates composed of one-input and one-output modules, 5 AND gate modules with three-input and one-output, 8 AND gate modules with two-input and one-output, 5 OR gate modules with two-input and one-output, 7 fan-out gates and 5 fluorescence reporting gates.
[0103] Suppose the domain encoding molecular chain of input chain X0, X1, X2, X3 is<a0^1a1^T^b0^0b1^> ,<a2^1a3^T^b2^0b3^> ,<a4^1a5^T^b4^0b5^> ,<a6^1a7^T^b6^0b7^> , representing the logic value 0000; after inverting the input chain X0, X1, X2, and X3 through the NOT gate, an input chain with the opposite logic value can be obtained. A fan-out gate fans out a single chain with the same logical value.
[0104] Preferably, it also includes building an AND gate, an OR gate logic operation module, a fan-out gate, and a fluorescence reporter gate molecular circuit, and obtaining an output fluorescent chain OUTL01()= after DNA chain replacement.<m1^0m2^fluor01> Represents logical value 0, OUTL12()=<n1^1n2^fluor12> Represents logical value 1, OUTL21()=<p1^0p2^fluor21> Represents logical value 0, OUTL31()=<q1^0q2^fluor31> Represents logical value 0, OUTL41()=<w1^0w2^fluor41> Represents the logical value 0.
[0105] The present invention provides a method for constructing a power addition logic circuit based on DNA domain coding, which has the following beneficial effects:
[0106] 1. The present invention utilizes DNA chain displacement technology, adopts a domain coding strategy, and designs a power addition operation molecular circuit in combination with an input mapping module. This design uses a domain coding strategy with better stability under the premise of utilizing hybridization pairing between DNA molecules, avoids using high and low concentrations to represent high and low logic values, and successfully solves the problem of erroneous output caused by the NOT gate by encoding the domain of the DNA signal chain and using coding "1" and coding "0" to distinguish the positive and negative logic values of the DNA chain.
[0107] 2. Based on domain coding, the present invention designs an input mapping module using the mathematical mapping principle, which can realize basic logical operations such as AND, OR and NOT. These modules can be used to build molecular circuits for power addition operations. The working process of DNA chain displacement reaction is verified and clarified through VisualDSD simulation software, and the expected function of power addition operation is realized. The results prove its effectiveness. It has faster reaction speed, better parallelism and packaging. Under the same experimental conditions, compared with the dual-track strategy, the potential of domain coding strategy in constructing large-scale complex logic circuits is demonstrated. BRIEF DESCRIPTION OF THE DRAWINGS
[0108] Figure 1 It is a flow chart of building a power addition molecular circuit of the present invention;
[0109] Figure 2 is the domain encoding rule of the DNA signal chain of the present invention;
[0110] Figure 3 It is a reaction mechanism diagram of the 2-input 1-output OR gate logic operation module of the present invention;
[0111] Figure 4 A logic circuit diagram of a four-bit square root of the present invention;
[0112] Figure 5 4-bit square root domain coding DSD simulation diagram of the present invention, wherein (a) is X4X3X2X1=0000 and Y0Y1=00, (b) is X4X3X2X1=0001 and Y0Y1=01, (c) is X4X3X2X1=0100 and Y0Y1=10, (d) is X4X3X2X1=1001 and Y0Y1=11;
[0113] Figure 6 A logic circuit diagram of the power addition operation of the present invention;
[0114] Figure 7 The domain coding DSD simulation diagram of the power addition operation of the present invention, wherein (a) is X3X2X1X0=0000 and Y4Y3Y2Y1Y0=00010; (b) is X3X2X1X0=0001 and Y4Y3Y2Y1Y0=00011; (c) is X3X2X1X0=0010 and Y4Y3Y2Y1Y0=00101; (d) is X3X2X1X0=0011 and Y4Y3Y2Y1Y0=01001; (e) is X3X2X1X0=0101 and Y4Y3Y 2Y1Y0=00100, (f) is X3X2X1X0=0110 and Y4Y3Y2Y1Y0=00110, (g) is X3X2X1X0=0111 and Y4Y3Y2Y1Y0=01010, (h) is X3X2X1X0=1010 and Y4Y3Y2Y1Y0=01000, (i) is X3X2X1X0=1011 and Y4Y3Y2Y1Y0=01100, (j) is X3X2X1X0=1111 and Y4Y3Y2Y1Y0=10000. DETAILED DESCRIPTION
[0115] The following will be combined with the drawings in the specification of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.
[0116] Example:
[0117] Please refer to the attached Figure 1-7 , an embodiment of the present invention provides a method for constructing a power addition operation logic circuit based on DNA domain encoding, comprising the following steps:.
[0118] Step 1: Propose a domain coding strategy based on the chain structure of DNA to encode the special domains of the DNA chain, instead of using the high and low concentrations of the DNA chain to represent positive and negative logical values.
[0119] like Figure 2 As shown in the figure, a domain coding strategy is proposed based on the chain structure characteristics of DNA. The main purpose is to divide the DNA signal chain centered on the toehold T into two parts, the left part can be complementary paired with the same domain structure of the upstream signal chain, and the right part determines the logic value of each single chain; according to the different domains of the DNA chain, its domain can be encoded into four codes: (0, 0), (0, 1), (1, 0), (1, 1), and code 0 corresponds to the logic value "0", and code 1 represents the logic value "1". If the right side code is "0", it means that the logic value of the DNA chain is negative, and if the right side code is "1", it means that the logic value of the DNA chain is positive. For example, the domain coding structure of the DNA chain can be designed as: A0()=<a^0b^T^c^0d^> ,A1()=<a^0b^T^c^1d^> ,A2()=<a^1b^T^c^0d^> ,A3()=<a^1b^T^c^1d^> Among them, T^ is the small branch domain, and <> represents the upper chain structure part of the DNA chain.
[0120] Step 2: Use domain coding strategy to construct domain coding fan-out gates, domain coding amplifiers and fluorescence reporter gates.
[0121] The fan-out gate constructed using the domain encoding strategy is mainly composed of four double chains (labeled as F01, F02, F03, F04) and two fuel chains (H0, H1). The double chain structure of the fan-out gate can be designed as: F01()={T^*}[a^0b^T^]<e^0f^> , F02()={T^*}[a^1b^T^]<e^1f^> , F03()={T^*}[a^0b^T^]<g^0k^> , F04()={T^*}[a^1b^T^]<g^1k^> , the fuel chain structure can be designed as: H0()=<a^0b^T^hL^h hR^> ,H1()=<a^1b^T^hL^h hR^> Among them, T^ is a small branch domain, <> represents the upper chain structure part of the DNA chain, [] represents the double-stranded structure part of the DNA chain that has been complementary paired, : represents the double-stranded structure domain used to connect the two parts, {} represents the lower chain structure part of the DNA chain, ^ is used to mark the upper chain domain, and ^* is used to mark the lower chain domain.
[0122] The reaction equation of domain coding 2-fan-out door is as follows:
[0123] A0+F01→sp8+output1 (1)
[0124] A0+F02→sp8+output2 (2)
[0125] A0+F03→sp10 (3)
[0126] A0+F04→sp9 (4)
[0127] H0+sp8→sp7+A0 (5)
[0128] Reaction equations (1)-(4) are the reaction process between the input chain A0 and the domain encoding fan-out double chain F01-F04. A0 and F01-F04 on the left side of the arrow are the reactants, and the right side of the arrow is the new product. The forward reaction rate and the reverse unbinding rate are set to 3.0e-4nM, respectively. -1 s -1 and 0.1126s -1 . The chain displacement reaction processes involved later are all set for this rate and will not be repeated. Since the input chain A0 represents the logical value "0", the double-chain domains F01 and F02 fan out two single chains output1 and output2 representing the logical value 0 after chain displacement with A0, while the double-chain domains F03 and F04 can only output hybrid double-chain structures sp10 and sp9 after chain displacement with A0. The input chain A0 plays a catalytic role. As long as sufficient concentration is added, the fan-out door double chain can be activated to react. Reaction formula (5) is the reaction process between the fuel chain H0 and the waste sp8, and the input chain A0 is regenerated on the right side of the arrow. At this time, the concentration of the A0 input chain can be set equal to the concentration of the fan-out door double chain, and the double chains of all fan-out doors are set equal. In order to make the concentration of the output chain reach a higher level, the concentration of the fuel chain is set to twice the sum of the concentrations of all fan-out door double chains.
[0129] The domain coding amplifier in step 2 is mainly composed of two double chains Amp0 and Amp1, and two fuel chains H0 and H1. The Amp0 double chain is designed as {T^*}[a1^0a2^T^]<c1^0c2^> , combined with H0 to complete the task of amplifying logic 0, the Amp1 double chain design is {T^*}[a1^1a2^T^]<c1^1c2^> , combined with H1 to complete the amplification task of logic 1. The main reason for adding an amplifier is that in the DNA chemical reaction network, the concentration of the DNA signal chain decays as the reaction proceeds, which will eventually slow down the reaction speed of the entire system. Therefore, it is necessary to add an amplifier at the appropriate position of the reaction network to amplify the concentration of the signal chain to be output to a high concentration before passing it to the downstream module.
[0130] The reaction equation of the domain coding amplifier is as follows:
[0131] A0+Amp0→sp10+out (6)
[0132] A0+Amp1→sp11 (7)
[0133] H0+sp10→sp6+A0 (8)
[0134] H1+sp10→sp7 (9)
[0135] Reaction equations (6)-(7) are the reaction process between the input chain A0 representing the logic value "0" and the double chain of the domain coding amplifier. Here, the input chain concentration is set to 1x (1x = 10 3 nM), the amplifier double-strand concentration is set to 1x, and the fuel chain concentration is set to 2 times the double-strand concentration. The input chain A0 undergoes a chain displacement reaction with the double-stranded Amp1 and Amp2 at the same time through the middle foothold T. Only the single-stranded out is formed in the reaction path with Amp0, and Amp1 only produces the intermediate product sp11, and no single-stranded is produced, because the long-chain domain of A0 does not have a complementary pairing part with Amp1; at this time, the logic value of the single-stranded out remains the same as the logic value of the input chain A0, both representing the logic value "0", but its concentration is raised to 1x concentration again.
[0136] If the input signal chain A1 has a logic value of "1", the input chain A1 undergoes a chain displacement reaction with the double-chain Amp0 and Amp1 at the same time through the middle foothold T. Only a single chain is formed in the reaction path with Amp1, and Amp0 only produces an intermediate product, and no single chain is produced, because the long chain domain of A1 does not have a complementary pairing part with Amp0; the output single chain logic value remains the same as the logic value of the input chain A1, both represent a logic value of "1", and the concentration is raised to 1x concentration. Reaction equations (8)-(9) are the process in which the fuel chains H0 and H1 undergo chain displacement with the intermediate product chain sp10 at the same time, and the input chain A0 is regenerated after displacement with H0.
[0137] It can be seen that in the entire reaction process, the domain-encoded single strand is produced when and only when one input strand reacts with one amplifier double strand, and although the other double strand participates in the reaction, only an intermediate product is obtained in the end.
[0138] The fluorescent reporter gate in step 2 is mainly used to convert the output signal chain into a fluorescent signal that is easy to detect. The domain-coded fluorescent reporter gate is composed of two double chains Rep0 and Rep1. The single-chain part on the right side of the double chain is a fluorescent detection domain with a fluorescent quenching group. By detecting the coding domain on the fluorophore, the output logic value can be known, and the output chain result can be converted into a fluorescent signal of different colors.
[0139] The reaction equation for the domain-encoded fluorescent reporter gate is shown below:
[0140] Out+Rep0→sp6+rep (10)
[0141] Out+Rep1→sp5 (11)
[0142] Reaction (10) is the reaction process between the output chain Out and the fluorescent reporter chain Rep0. After the output chain reacts with the reporter chain, the intermediate products sp6 and rep on the right are generated. Rep is a fluorescent output chain with a fluorophore, and the coding domain of the fluorescent chain can be detected to obtain the logical value. Reaction (11) is the reaction process between the output chain Out and the fluorescent reporter chain Rep1. The intermediate product sp5 is obtained on the right side of the reaction, but no fluorescent signal chain falls off.
[0143] Step 3: Construct a domain coding logic operation module, such as a one-input one-output logic operation module, a two-input one-output logic operation module, a three-input one-output logic operation module, and an N-input one-output logic operation module.
[0144] The domain coding logic operation module in step 3 can be divided into: one-input one-output logic operation module, two-input one-output logic operation module, three-input one-output logic operation module and N-input one-output logic operation module according to the number of input terminals. The main basis of these operation modules is obtained according to the mapping relationship in mathematics. The number of DNA double strands and the length of the double-stranded domain are determined according to the number of input terminals, and the logic function is determined by programming the logic value of the double-stranded domain.
[0145] The one-input one-output logic operation module is composed of two DNA double strands, which can be designed as {T^*}[a^0b^T^]<e^k1f^> and {T^*}[a^1b^T^]<e^k2f^> , k1 and k2 on the single-chain domain can be encoded, and there are 22=4 encoding situations. When k1 and k2 are (0,0), the reset function is realized; when k1 and k2 are (0,1), the YES gate function is realized; when k1 and k2 are (1,0), the NOT gate function is realized; when k1 and k2 are (1,1), the set 1 function is realized. The reaction process of the NOT gate of the one-input and one-output logic operation module is as follows:
[0146] A0+F01→sp5+output (12)
[0147] A0+F02→sp6 (13)
[0148] Reaction formulas (12)-(13) are the reaction process of using an input logic operation module to realize the inversion of the logic value of input chain A0. The right coding domain of input chain A0 takes the value 0, representing the logic value "0". After entering the reaction pool, it is hybridized and paired with double chains F01 and F02 at the same time. After A0 is paired with F01, a single chain out and waste sp5 are generated. The logic value of the detached single chain out is exactly opposite to the logic value of the input chain A0, realizing the NOT gate function. After pairing with F02, no single chain is detached, and only a double chain sp6 is generated. It can be seen from the reaction that only the right domain of single chain A0 can be complementary to the middle domain of the double chain F01, and there is no complementary part with F02, so chain displacement will not occur, and chain detachment will not occur.
[0149] Secondly, the two-input one-output logic operation module consists of 2 2 = 4 DNA double strands, DNA double strands can be designed as F01 = {T^*} [a^0b^T^c^0d^]<e^k1f^> 、F02={T^*}[a^0b^T^c^1d^]<e^k2f^> , F03 = {T^*}[a^1b^T^c^0d^]<e^k3f^> , F04 = {T^*}[a^1b^T^c^1d^]<e^k4f^> , k1, k2, k3, k4 on the single-chain domain can encode 2 4 =16 cases. When k1, k2, k3, k4 are (0, 0, 0, 0), the reset function is realized; when k1, k2, k3, k4 are (0, 0, 0, 1), the AND function is realized; when k1, k2, k3, k4 are (1, 1, 1, 0), the AND function can be realized; when k1, k2, k3, k4 are (0, 1, 1, 1), the OR function can be realized; when k1, k2, k3, k4 are (1, 0, 0, 0), the OR function can be realized; when k1, k2, k3, k4 are (0, 1, 1, 0), the XOR function can be realized; when k1, k2, k3, k4 are (1, 0, 0, 1), the XOR function can be realized; when k1, k2, k3, k4 are (1, 1, 1, 1), the reset function is realized.
[0150] like Figure 3 As shown, the reaction mechanism of the two-input and one-output logic operation module or gate is as follows:
[0151] A0+F01→sp27 (14)
[0152] A0+F02→sp26 (15)
[0153] A0+F03→sp25→sp23+waste1 (16)
[0154] A0+F04→sp24→sp21+waste1 (17)
[0155] A1+sp23→sp20 (18)
[0156] A1+sp21→sp19→sp17+sp18 (19)
[0157] sp17+amp1→sp14+sp15 (20)
[0158] sp14+Report→rep+waste2 (21)
[0159] The specific steps of the reaction process of reaction formula (14)-(21) are as follows: A0 and A1 are two input signal chains, representing logic value 0 and logic value 1 respectively. Input chain A0 first reacts with four double chains F01-F04 simultaneously to generate hybrid double chains sp27, sp26, sp25, and sp24 respectively, and the double-chain structures of sp25 and sp24 continue to be replaced by sp23, sp21 and an identical waste waste1. At this time, input chain A1 begins to undergo chain replacement reaction with sp23 and sp21 to generate hybrid double chains sp20 and sp19, and sp19 continues to split into single chains sp17 and sp18. Sp17 is used as an output chain to react with the amplifier gate double chain amp1 to generate single chain sp14 and double chain sp15. Sp14 reacts with the fluorescent reporter gate to output the final fluorescent signal chain out. The logical value of this fluorescent signal chain is 1, which meets the logical function of the OR gate.
[0160] The three-input and one-output logic operation module consists of 2 3 =8 DNA double strands, DNA double strands can be designed as F01 = {T^*}[a^0b^T^c^0d^T^e^0f^]<g^k1k^> , F02={T^*}[a^0b^T^c^0d^T^e^1f^]<g^k2k^> , F03={T^*}[a^0b^T^c^1d^T^e^0f^]<g^k3k^> , F04={T^*}[a^0b^T^c^1d^T^e^1f^]<g^k4k^> , F05={T^*}[a^1b^T^c^0d^T^e^0f^]<g^k5k^> , F06={T^*}[a^1b^T^c^0d^T^e^1f^]<g^k6k^> , F07={T^*}[a^1b^T^c^1d^T^e^0f^]<g^k7k^> , F08={T^*}[a^1b^T^c^1d^T^e^1f^]<g^k8k^> , k1, k2, k3, k4, k5, k6, k7, k8 on the single-chain domain can be encoded as 2 8 = 256 cases. When k1, k2, k3, k4 are (0, 1, 1, 1, 1, 1, 0), the XOR function can be realized. When k1, k2, k3, k4 are (0, 1, 1, 0, 1, 0, 0, 1), the full adder summation (full subtractor difference) function can be realized.
[0161] Based on the above method for constructing a logic operation module, any n-input-one-output logic operation module can be constructed according to circuit requirements.
[0162] Step 4: Use the domain coded logic operation module to build a DNA circuit for calculating the four-digit square root. Use the DSD simulation software to verify its correctness and make a comparative analysis with the four-digit square root circuit built with two tracks.
[0163] In step 4, the DNA circuit for calculating the four-digit square root is constructed by using the domain coding logic operation module, and the typical four input values 0, 1, 4, and 9 are calculated. First, the logic circuit diagram of the four-digit square root is constructed according to the truth table, as shown in FIG. Figure 4 As shown in the figure, it consists of 4 NOT gates, 4 AND gates and an OR gate; then the domain coding logic operation module is determined according to the logic circuit diagram. The DNA circuit for building a four-bit square root needs to be composed of 4 logic NOT gates, 3 three-input logic AND gates, 1 two-input logic OR gate and 1 two-input logic AND gate. Corresponding to the above domain coding logic operation module idea, one-input, two-input and three-input logic operation modules are used to implement it.
[0164] First, the input signals A0, A1, A2, and A3 are inverted through the logic NOT gate to obtain
[0165] Then use 3 domain encoding fan-out gates to input chain A0, Perform fan-out operation to obtain signal chains with the same logic value. For example, the encoding structures of input chains A0, A1, A2, and A3 are<i1L^b i1R^T^m1L^a m1R^> ,<i2L^b i2R^T^m2L^a m2R^> ,<i3L^b i3R^T^m3L^a m3R^> ,<i3L^b i3R^T^m4L^a m4R^> , all represent logical value 0. The specific reaction process of the 4 input chains being inverted through the logic NOT gate is as follows:
[0166] A0+NA0→sp94+sp91 (22)
[0167] A1+NA1→sp89+sp90 (23)
[0168] A2+NA2→sp87+sp88 (24)
[0169] A3+NA3→sp85+sp86 (25)
[0170] Reaction formulas (22)-(25) use a one-input one-output logic operation module to implement the reaction process of inverting the logic value of input chain A0. In reaction formula (22), after input chain A0 is paired with double-stranded NA0, single-stranded sp94 is generated, which is encoded as<m1L^am1R^T^u1L^b u1R^> and waste sp91, the logic value of the detached single-stranded sp94 is opposite to the logic value of the input chain A0, representing a logic value of 1; the reaction process of reaction formulas (23)-(25) is similar to reaction formula (22), and single-stranded sp89 is produced, which is encoded as<m2L^a m2R^T^u2L^b u2R^> , sp87 is encoded as<m3L^a m3R^T^u3L^b u3R^> and sp85 is encoded as<m4L^am4R^T^u4L^b u4R^> , which is opposite to the logic value of input chain A1, A2, and A3, and all represent logic value 1.
[0171] Use 3 domain encoding fan-out gates to input chain A0, Perform a fan-out operation. The specific reaction process is as follows:
[0172] A0+IFA0→sp93+sp94 (26)
[0173] A0+IFA1→sp92+sp94 (27)
[0174] A1+NA1→sp89+sp90 (28)
[0175] sp89+NFA10→sp82+sp83 (29)
[0176] sp89+NFA11→sp81+sp83 (30)
[0177] A2+NA2→sp87+sp88 (31)
[0178] sp87+NFA20→sp79+sp80 (32)
[0179] sp87+NFA21→sp78+sp80 (33)
[0180] Reaction formulas (26)-(27) respectively fan out two single chains sp92 and sp93 with the same logic value as A0, both representing logic value 0; reaction formula (28) reverses the logic value of A1 single chain representing logic value 0 to obtain sp89 single chain representing logic value 1. In reaction formulas (29)-(30), sp89 single chain reacts with fan-out gate double chains NFA10 and NFA11 respectively, fanning out two single chains sp81 and sp82 with the same logic value. The structure of sp81 single chain is<u2L^bu2R^T^b2L^bb2R^> , representing a logical value of 1, and the single-chain structure of sp82 is<u2L^bu2R^T^b1L^bb1R^> , representing the logical value 1.
[0181] Reaction (31) inverts the logic value of the A2 single chain representing the logic value 0 to obtain the sp87 single chain representing the logic value 1. In reactions (32)-(33), the sp87 single chain reacts with the fan-out gate double chains NFA20 and NFA21 respectively, fanning out two single chains sp78 and sp79 with the same logic value. The structure of the sp78 single chain is<u3L^b u3R^T^b4L^b b4R^> , representing a logical value of 1, and the single-chain structure of sp82 is<u3L^b u3R^T^b3L^b b3R^> , representing the logical value 1.
[0182] Secondly, two three-input and one-output logic AND gate modules, one two-input logic OR gate and one two-input logic AND gate are used to implement AND operation and realize the logic value output of Y1. The specific reaction process of the two three-input and one-output logic AND gate modules is as follows:
[0183]
[0184] In reaction formula (34), after the input chain A2 and the inverted input chains A0 and A3 react with the double-stranded chain F6 of the three-input one-output module, the double-stranded structure of F6 is {T^*}[u4L^b u4R^T^]:[m3L^a m3R^T^]:[u1L^b u1R^T^]<c1L^a c1R^> , producing single-stranded sp60 and waste, the generated sp60 single-stranded<u1L^b u1R^T^c1L^a c1R^> ; In reaction formula (35), input chains A0, A3 and input chain After the double-stranded F11 of the three-input and one-output module reacts, single-stranded sp60 and waste are produced. The double-stranded structure of F11 is {T^*}[m4L^a m4R^T^]:[b3L^b b3R^T^]:[a1L^a a1R^T^]<c2L^a c2R^> The resulting sp64 single chain is<a1L^a a1R^T^c2L^a c2R^> .
[0185] The single-chain sp60 and sp64 obtained after the operation of the two logic and modules enter the two-input and one-output logic or gate module for logic or operation. The specific reaction process is as follows:
[0186] sp60+H1→sp55+waste (36)
[0187] sp64+sp55→sp49+waste (37)
[0188] H1 in reaction (36) is a double chain of two-input and one-output logic OR gates, and its encoding structure is {T^*}[c1L^ac1R^T^]:[c2L^a c2R^T^]<d1L^a d1R^> , with single-chain sp60<u1L^b u1R^T^c1L^a c1R^> After strand displacement, sp55 single strand is formed; in reaction equation (37), sp55 and sp64 single strands are<a1L^a a1R^T^c2L^a c2R^> After strand displacement, a single-stranded sp49 is obtained, and the strand structure of sp49 is<c2L^a c2R^T^d1L^a d1R^> .
[0189] After the logic OR gate module operation, the generated single chain sp49 and the input chain The single-chain sp82 enters the two-input and one-output logic AND gate module for further AND operation. The specific reaction process is as follows:
[0190] sp49+H6→sp46+waste (38)
[0191] sp46+sp82→sp43+waste (39)
[0192] H6 in reaction (38) is a double chain of two-input and one-output logic AND gates, and its encoding structure is {T^*}[d1L^ad1R^T^]:[b1L^b b1R^T^]<d2L^a d2R^> , after reacting with single-stranded sp49, a double-stranded sp46 output and waste are obtained; in reaction formula (39), the double-stranded sp46 reacts with the single-stranded sp82 to produce a single-stranded sp43, and its encoding structure is<b1L^b b1R^T^d2L^a d2R^> .
[0193] The sp43 single chain obtained after the above logic operation reaction output is further amplified through the amplification gate. The specific amplification reaction process is as follows:
[0194] sp43+amp11→sp41+sp42 (40)
[0195] In reaction formula (40), amp11 is a double chain of the amplification gate, and its structure is {T^*}[d2L^a d2R^T^]<pL^a pR^> After passing through the amplification gate, a single chain of sp41 and waste sp42 are generated. The single chain structure of sp41 is<d2L^a d2R^T^pL^a pR^> .
[0196] In order to more conveniently observe the output logic value, the single-chain sp41 is output in the form of a fluorescent chain, which is realized through the fluorescent reporting gate Report. The specific reaction process is as follows:
[0197] sp41+ReportL11→OUTL11+sp39 (41)
[0198] ReportL11 in reaction formula (41) is the double chain of the fluorescent gate, and its structure is {T^*}[pL^a pR^] <fluor01>After passing through the fluorescent reporter gate, the single-stranded OUTL11 and the waste sp39 are generated. The single-stranded structure of OUTL11 is [pL^a pR^] <fluor01>, the output fluorescent chain logical value represents 0.
[0199] Finally, a three-input and one-output logic AND gate module is used to realize the logic value output of Y0. The reaction process is as follows:
[0200] sp78+B7→sp68+sp69 (42)
[0201] sp69+sp81→sp63+sp62 (43)
[0202] sp63+sp92→sp56+sp57 (44)
[0203] In reaction formula (42), B7 is a domain-encoded double chain of a three-input and one-output AND gate, and its structure is {T^*}[b4L^bb4R^T^]:[b2L^b b2R^T^]:[a2L^a a2R^T^]<c3L^a c3R^> , after the sp78 single strand and the B7 double strand undergo strand displacement, a sp69 double strand mixture and waste sp68 are produced; in reaction formula (43), after the sp69 double strand mixture and the sp81 single strand undergo strand displacement, waste sp62 and a double strand mixture sp63 are produced; in reaction formula (44), after the double strand mixture sp63 and the sp92 single strand undergo strand displacement, a sp56 single strand and a sp57 double strand mixture are produced, wherein sp56 is the desired single strand output, and its strand structure is<a2L^a a2R^T^c3L^a c3R^> .
[0204] The single-stranded sp56 continues to be amplified through the amplification gate, and then output in the form of a fluorescent chain through the fluorescence reporter gate. The specific reaction process is as follows:
[0205] sp56+amp21→sp51+sp52 (45)
[0206] sp51+ReportL21→sp47+OUTL21 (46)
[0207] In reaction formula (45), amp21 is a double-stranded amplification gate, and its structure can be set as {T^*}[c3L^a c3R^T^]<zL^azR^> After chain displacement with single-stranded sp56, sp51 single-stranded and sp52 double-stranded wastes are generated. The chain structure of sp51 is<c3L^ac3R^T^zL^a zR^> In reaction equation (46), after strand displacement between sp51 and the fluorescent reporter gate ReportL21, double-stranded waste sp47 and fluorescent chain OUTL21 are generated. The chain structure of OUTL21 is<zL^a zR^fluor11> The output fluorescent chain OUTL21 has a logic value of 0.
[0208] The simulation results are as follows Figure 5 As shown in (a), the two fluorescent chains OUTL11 and OUTL21 output high-concentration fluorescence curves, reaching the maximum value at 60s, representing the output result of 00. When the logic value of the above input chain is 0000, the corresponding four-digit square root calculation result is consistent. Figure 5 (b)-(d) show that when the input values are 1, 4, and 9, respectively, the values of the fluorescence output chain after taking the square root are 1, 2, and 3.
[0209] Compared with the four-digit square root circuit designed with a dual-track circuit, when the initial parameters of the species are set to be consistent, the initial reactants of the four-digit square root circuit designed with domain coding are reduced from 130 to 61, and the reaction time is reduced to 1 / 24 of that of the dual-track circuit. The circuit construction is simpler and the output results are more stable.
[0210] Step 5: Use the domain coded logic operation module to build a DNA circuit for power addition operation, verify its correctness with the DSD simulation software, and make a comparative analysis with the power addition DNA operation circuit built with dual tracks.
[0211] The method of the power addition numerator circuit in step 5 is: obtain the truth table of the power addition operation logic circuit through the logical relationship, and construct the power addition logic circuit according to the truth table. The power addition logic circuit is mainly composed of 4 NOT gates, 13 AND gates, and 5 OR gates. Figure 6 shown.
[0212] The output expression of the power addition logic circuit is:
[0213]
[0214] Y 4 =X 3 X 2 X 1 X 0
[0215] The domain coding logic operation module and the power addition logic circuit are used to construct the power addition numerator circuit, which can realize the addition operation of 2x and 2x (x is 0-3). For example, 2 0 with 2 3 The addition operation.
[0216] The power addition molecular operation circuit consists of 4 NOT gates composed of one-input and one-output modules, 5 AND gate modules with three inputs and one output, 8 AND gate modules with two inputs and one output, 5 OR gate modules with two inputs and one output, 7 fan-out gates and 5 fluorescence reporter gates. The domain encoding molecular chains of the input chains X0, X1, X2, and X3 are<a0^1a1^T^b0^0b1^> ,<a2^1a3^T^b2^0b3^> ,<a4^1a5^T^b4^0b5^> ,<a6^1a7^T^b6^0b7^> , representing the logical value 0000;
[0217] Changing the domain code of the input chain can change the logical input value of the input chain. The output value Y1Y2Y3Y4 is represented by the fluorescent signal chain, and the logical value code of the output signal can be designed as<m1^0m2^fluor02> ,<n1^0n2^fluor11> ,<p1^0p2^fluor21> ,<q1^1q2^fluor32> ,<w1^0w2^fluor41> , indicating that the output logic value is 00010.
[0218] According to the logic operation module construction method, the corresponding number of NOT gate, AND gate, OR gate logic operation modules, as well as fan-out gate and fluorescence reporter gate molecular circuits are built. The concentration of the input signal chain and the domain-coded double strand is set to 1000nM. Since the domain-coded fan-out gate contains N double strands and 1 fuel chain, in order to better catalyze the output of the DNA signal chain, the concentration of the fuel chain is set to twice the sum of the fan-out double strand concentrations. For example, if the number of fan-out gates is set to 2, the concentration of the fuel chain is set to 4 times the concentration of the fan-out double strand. If the number of fan-out gates is set to 3, the concentration of the fuel chain is set to 6 times the concentration of the fan-out double strand, and so on. The concentration of the DNA double strand in the logic operation module and the fluorescence reporter gate is set to 1000nM, and the concentration of the fuel chain in the domain-coded amplifier is set to twice the concentration of the double strand in the amplifier. After setting the concentration, the DNA chain displacement reaction is completed through the DSD simulation software to obtain the fluorescent output chain result.
[0219] DSD simulation results are as follows Figure 7 As shown, in Figure 7 In (a), the output curves of OUTY01, OUTY12, OUTY21, OUTY31, and OUTY41 gradually rise from 0 nM to a high concentration stage of nearly 1000 nM, and slide into a steady state after 1500 seconds, indicating a logical value of "1", while the output curves of OUTY02, OUTY11, OUTY22, OUTY32, and OUTY42 coincide with the horizontal axis. We consider the output to be logical "0", and the final logical output value of Y0 is "00010", which is equal to 2 0 and 2 0 The result of the power addition operation between .
[0220] exist Figure 7 In (b), the curves of OUTY02, OUTY12, OUTY21, OUTY31, and OUTY41 represent the output logic value "00011", and the output curves of OUTY01, OUTY11, OUTY22, OUTY32, and OUTY42 are overlapped on the horizontal axis. We consider them to be logic "0", which is equal to 2 0 To 2 1 The result of the power addition operation between .
[0221] exist Figure 7 In (c), the output curves of OUTY02, OUTY11, OUTY22, OUTY31, and OUTY41 represent the output logic value "00101". The output curves of OUTY01, OUTY12, OUTY21, OUTY32, and OUTY42 coincide with the horizontal axis, and we consider them to be logic "0", which is equal to 2 0 To 2 2 The result of the power addition operation between .
[0222] Figure 7 The curves of OUTY02, OUTY11, OUTY21, OUTY32, and OUTY41 in (d) represent the output logic value "01001". The output curves of OUTY01, OUTY12, OUTY22, OUTY31, and OUTY42 coincide with the horizontal axis, so we consider them to be logic "0", which is equal to 2. 0 To 2 3 The result of the power addition operation between .
[0223] exist Figure 7 In (e), the curves of OUTY01, OUTY11, OUTY22, OUTY31, and OUTY41 represent the output logic value "00100", and the output curves of OUTY02, OUTY12, OUTY21, OUTY32, and OUTY42 coincide with the horizontal axis, which we regard as logic "0", which is equal to 2 1 To 2 1 The result of the power addition operation between .
[0224] exist Figure 7 In (f), the curves of OUTY01, OUTY12, OUTY22, OUTY31, and OUTY41 represent the output logic value "00110", and the output curves of OUTY02, OUTY11, OUTY21, OUTY32, and OUTY42 coincide with the horizontal axis, which we regard as logic "0", which is equal to 2 1 To 2 2 The result of the power addition operation between .
[0225] exist Figure 7 In (g), the curves of OUTY01, OUTY12, OUTY21, OUTY32, and OUTY41 represent the output logic value "01010". OUTY02, OUTY11, OUTY22, OUTY31, and OUTY42 coincide with the horizontal axis, and we consider them to be logic "0", which is equal to 2 1 To 2 3 The result of adding the powers of .
[0226] exist Figure 7 In (h), the curves of OUTY01, OUTY11, OUTY21, OUTY32, and OUTY41 represent the output logic value "01000", and the output curves of OUTY02, OUTY12, OUTY22, OUTY31, and OUTY42 coincide with the horizontal axis, which we regard as logic "0", which is equal to 2 2 and 2 2 The result of the power addition operation between .
[0227] exist Figure 7 In (i), the curves of OUTY01, OUTY11, OUTY22, OUTY32, and OUTY41 represent the output logic value "01100", and the output curves of OUTY02, OUTY12, OUTY21, OUTY31, and OUTY42 coincide with the horizontal axis, which we regard as logic "0", which is equal to 2 2 and 2 3 The result of the power addition operation between .
[0228] exist Figure 7 In (j), the curves of OUTY01, OUTY11, OUTY21, OUTY31, and OUTY42 represent the output logic value "10000", respectively. The output curves of OUTY02, OUTY12, OUTY22, OUTY32, and OUTY41 coincide with the horizontal axis, which we regard as logic "0", which is equal to 2. 3 and 2 3 The result of the power addition operation between .
[0229] Under the same simulation conditions, a power addition molecular circuit in dual-track mode was built, and a comparative analysis was conducted with the domain-encoded power addition molecular circuit in terms of circuit structure, reaction time, and the number of participating chains. The specific contents are as follows:
[0230] The power addition molecular circuit constructed by the dual-track strategy consists of 28 logic gates, while the domain-encoded molecular circuit only needs 18 switches, which is simpler in structure than the dual-track circuit. The dual-track logic circuit has more than 110 reactants involved in the reaction, while the DNA switch circuit involves 62 reactants in one calculation, which is nearly 43% less reactants. A comparison of the reaction time shows that the dual-track circuit takes more than 5000s to complete the calculation, while the DNA switch circuit only takes 1500s. These results show that compared with the dual-track circuit, the domain-encoded molecular circuit has fewer reactants, faster calculation speed, simpler structure, and has more advantages in expanding the field of biological computing.
[0231] Although embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions and variations may be made to the embodiments without departing from the principles and spirit of the present invention, and that the scope of the present invention is defined by the appended claims and their equivalents.
Claims
1. A method for constructing a power addition logic circuit based on DNA domain coding, characterized in that: The following steps are involved: Step 1: Based on the DNA chain structure, a domain coding strategy is proposed to encode the special domains of the DNA chain, instead of using the high and low concentrations of the DNA chain to represent positive and negative logic values; Step 2: Use domain coding strategy to construct domain coding fan-out gates, domain coding amplifiers, and fluorescence reporter gates; Step 3: construct a domain coding logic operation module, such as a one-input one-output logic operation module, a two-input one-output logic operation module, a three-input one-output logic operation module, and an N-input one-output logic operation module; Step 4: Use the domain coded logic operation module to build a DNA circuit for calculating the four-digit square root. Use the DSD simulation software to verify its correctness and make a comparative analysis with the four-digit square root circuit built with two tracks. Step 5: Use the domain coded logic operation module to build a DNA circuit for power addition operation, verify its correctness with the DSD simulation software, and make a comparative analysis with the power addition DNA operation circuit built with dual tracks.
2. According to claim 1, a method for constructing a power addition logic circuit based on DNA domain coding is characterized in that: The domain coding strategy in step 1 is to divide the DNA signal chain centered on the toehold T into two parts, the left part can be complementary paired with the same domain structure of the upstream signal chain, and the right part determines the logic value of each single chain; according to the different domain codes, the DNA single chain can encode the domain into four codes: (0, 0), (0, 1), (1, 0), (1, 1), code 0 corresponds to the logic value "0", code 1 represents the logic value "1", if the right side code is "0", it means that the logic value of the DNA chain is negative, if the right side code is "1", it means that the logic value of the DNA chain is positive. The domain coding structure of the DNA chain is designed as: A0()=<a^0b^T^c^0d^> ,A1()=<a^0b^T^c^1d^> ,A2()=<a^1b^T^c^0d^> ,A3()=<a^1b^T^c^1d^> Among them, T^ is the small branch domain, and <> represents the upper chain structure part of the DNA chain.
3. The method for constructing a power addition logic circuit based on DNA domain coding according to claim 1, characterized in that: The fan-out gate constructed using the domain encoding strategy in step 2 is composed of four double chains (labeled as F01, F02, F03, F04) and two fuel chains (H0, H1). The double chain structure is designed as: F01()={T^*}[a^0b^T^]<e^0f^> , F02()={T^*}[a^1b^T^]<e^1f^> , F03()={T^*}[a^0b^T^]<g^0k^> , F04()={T^*}[a^1b^T^]<g^1k^> , the fuel chain structure is designed as: H0()=<a^0b^T^hL^h hR^> ,H1()=<a^1b^T^hL^hhR^> ; Wherein, T^ is a small branch point domain, <> represents the upper chain structure part of the DNA chain, [] represents the double-stranded structure part of the DNA chain that has been complementary paired, : represents the double-stranded structure domain used to connect two parts, {} represents the lower chain structure part of the DNA chain, ^ is used to mark the upper chain domain, and ^* is used to mark the lower chain domain; The reaction equation of domain coding 2-fan-out door is as follows: A0+F01→sp8+output1(1) A0+F02→sp8+output2(2) A0+F03→sp10(3) A0+F04→sp9(4) H0+sp8→sp7+A0(5) Reaction equations (1)-(4) are the reaction process between the input strand A0 and the domain-encoded fan-out double strands F01-F04. A0 and F01-F04 on the left side of the arrow are the reactants, and the new product is on the right side of the arrow. The forward reaction rate and reverse unbinding rate of DNA strand displacement are set to 3.0e-4nM, respectively. -1 s -1 and 0.1126s -1 , the subsequent reaction processes are all at this reaction rate. Reaction equation (5) is the reaction process between the fuel chain H0 and the waste sp8. The input chain A0 is regenerated on the right side of the arrow. At this time, the concentration of the A0 input chain can be set equal to the concentration of the double chain of the fan-outlet. The double chains of all fan-outlets are set equal. In order to make the concentration of the output chain higher, the concentration of the fuel chain is set to twice the sum of the concentrations of the double chains of all fan-outlets. The domain coding amplifier in step 2 is composed of two double chains Amp0 and Amp1, and two fuel chains H0 and H1. The Amp0 double chain is designed as {T^*}[a1^0a2^T^]<c1^0c2^> , combined with H0 to complete the task of amplifying logic 0, the Amp1 double chain design is {T^*}[a1^1a2^T^]<c1^1c2^> , combined with H1 to complete the task of amplifying logic 1. The reaction equation of the domain coding amplifier is as follows: A0+Amp0→sp10+out(6) A0+Amp1→sp11(7) H0+sp10→sp6+A0(8) H1+sp10→sp7(9) Reaction equations (6)-(7) are the reaction process between the input chain A0 representing the logic value "0" and the double chain of the domain coding amplifier. Here, the input chain concentration is set to 1xnM (1x = 10 3 nM), the concentration of the double-stranded amplifier was set to 1x nM (1x = 10 3 nM), the fuel chain concentration is set to twice the double-chain concentration, and the input chain A0 undergoes chain displacement reaction with the double-chain Amp1 and Amp2 at the same time through the middle foothold T. Only the single-chain out is formed on the reaction path with Amp0, and Amp1 only produces the intermediate product sp11, and no single-chain is produced; at this time, the logic value of the single-chain out remains the same as the logic value of the input chain A0, both representing the logic value "0", but its concentration is raised to 1x concentration again. If the input logic value of signal chain A1 is "1", the input chain A1 undergoes chain displacement reaction with the double chains Amp0 and Amp1 at the same time through the middle foothold T, and only a single chain is formed on the reaction path with Amp1, while Amp0 only produces an intermediate product, and no single chain is produced; the output single chain logic value remains the same as the logic value of the input chain A1, both representing the logic value "1", and the concentration is raised to 1xnM again. Reaction equations (8)-(9) are the process in which the fuel chains H0 and H1 undergo chain displacement with the intermediate product chain sp10 at the same time, and the input chain A0 is regenerated after displacement with H0; The fluorescent reporter gate in step 2 is used to convert the output signal chain into a fluorescent signal that is easy to detect. The domain-coded fluorescent reporter gate is composed of two double-chains Rep0 and Rep1. The single-chain part on the right side of the double-chain is a fluorescent detection domain with a fluorescent quenching group. The output logic value can be known by detecting the coding domain on the fluorophore, and the output chain result can be converted into a fluorescent signal of different colors; The reaction equation for the domain-encoded fluorescent reporter gate is shown below: Out+Rep0→sp6+rep(10) Out+Rep1→sp5(11) Reaction (10) is the reaction process between the output chain Out and the fluorescent reporter chain Rep0. After the output chain reacts with the reporter chain, the intermediate products sp6 and rep on the right are generated. Rep is a fluorescent output chain with a fluorophore. The coding domain of the fluorescent chain can be detected to obtain the logical value. Reaction (11) is the reaction process between the output chain Out and the fluorescent reporter chain Rep1. The intermediate product sp5 is obtained on the right side of the reaction, but no fluorescent signal chain falls off.
4. The method for constructing a power addition logic circuit based on DNA domain coding according to claim 1, characterized in that: The domain coding logic operation module in step 3 is divided into: a one-input one-output logic operation module, a two-input one-output logic operation module, a three-input one-output logic operation module and an N-input one-output logic operation module according to the number of input terminals. The main basis of these operation modules is obtained according to the mapping relationship in mathematics. The number of DNA double strands and the length of the double-stranded domain contained in the operation module are determined according to the number of input terminals, and the logic function is determined by programming the logic value of the double-stranded domain; The one-input one-output logic operation module is composed of two DNA double strands, and the DNA double strands are designed as {T^*}[a^0b^T^]<e^k1 f^> and {T^*}[a^1b^T^]<e^k2 f^> , k1 and k2 on the single-stranded domain are encoded by 2 2 =4 encoding situations, when k1, k2 are (0,0), the reset function is realized; when k1, k2 are (0,1), the YES gate function is realized; when k1, k2 are (1,0), the NOT gate function is realized; when k1, k2 are (1,1), the reset function is realized, and the reaction process of the NOT gate of the one-input and one-output logic operation module is as follows: A0+F01→sp5+out(12) A0+F02→sp6(13) Reaction formulas (12)-(13) use an input logic operation module to realize the reaction of inverting the logic value of input chain A0. The right coding domain of input chain A0 can take the value of 0, representing the logic value "0". After entering the reaction pool, it hybridizes and pairs with double chains F01 and F02 at the same time. After A0 is paired with F01, a single chain out and waste sp5 are generated. The logic value of the detached single chain out is exactly opposite to the logic value of the input chain A0, realizing the NOT gate function. After pairing with F02, no single chain is detached, and only a double chain sp6 is generated. The two-input one-output logic operation module consists of 2 2 = 4 DNA double strands, DNA double strands are designed as F01 = {T^*}[a^0b^T^c^0d^]<e^k1 f^> 、F02={T^*}[a^0b^T^c^1d^]<e^k2 f^> , F03 = {T^*}[a^1b^T^c^0d^]<e^k3 f^> , F04 = {T^*}[a^1b^T^c^1d^]<e^k4 f^> , k1, k2, k3, k4 on the single-chain domain can encode 2 4 =16 cases. When k1, k2, k3, k4 are (0, 0, 0, 0), the reset function is realized; when k1, k2, k3, k4 are (0, 0, 0, 1), the AND function is realized; when k1, k2, k3, k4 are (1, 1, 1, 0), the AND function can be realized; when k1, k2, k3, k4 are (0, 1, 1, 1), the OR function is realized; when k1, k2, k3, k4 are (1, 0, 0, 0), the OR function is realized; when k1, k2, k3, k4 are (0, 1, 1, 0), the XOR function is realized; when k1, k2, k3, k4 are (1, 0, 0, 1), the XOR function is realized; when k1, k2, k3, k4 are (1, 1, 1, 1), the reset function is realized. The reaction process of the two-input and one-output logic operation module or gate is as follows: A0+F01→sp27(14) A0+F02→sp26(15) A0+F03→sp25→sp23+waste1(16) A0+F04→sp24→sp21+waste1(17) A1+sp23→sp20(18) A1+sp21→sp19→sp17+sp18(19) sp17+amp1→sp14+sp15(20) sp14+Report→rep+waste2(21) The specific steps of the reaction process of the reaction formula are as follows: A0 and A1 are two input signal chains, representing logic value 0 and logic value 1 respectively. Input chain A0 first reacts with four double chains F01-F04 simultaneously to generate hybrid double chains sp27, sp26, sp25, and sp24 respectively, and the double-chain structures of sp25 and sp24 continue to be replaced by sp23, sp21 and an identical waste waste1. At this time, input chain A1 begins to undergo chain replacement reaction with sp23 and sp21 to generate hybrid double chains sp20 and sp19, and sp19 continues to split into single chains sp17 and sp18. Sp17 is used as an output chain to react with the amplifier gate double chain amp1 to generate single chain sp14 and double chain sp15. Sp14 reacts with the fluorescent reporter gate to output the final fluorescent signal chain rep. The logical value of this fluorescent signal chain is 1, which meets the logical function of the OR gate. The three-input and one-output logic operation module consists of 2 3 = 8 DNA double strands, DNA double strands are designed as F01 = {T^*}[a^0b^T^c^0d^T^e^0f^]<g^k1 k^> , F02={T^*}[a^0b^T^c^0d^T^e^1f^]<g^k2 k^> , F03={T^*}[a^0b^T^c^1d^T^e^0f^]<g^k3 k^> , F04={T^*}[a^0b^T^c^1d^T^e^1f^]<g^k4 k^> , F05={T^*}[a^1b^T^c^0d^T^e^0f^]<g^k5 k^> , F06={T^*}[a^1b^T^c^0d^T^e^1f^]<g^k6k^> , F07={T^*}[a^1b^T^c^1d^T^e^0f^]<g^k7 k^> , F08={T^*}[a^1b^T^c^1d^T^e^1f^]<g^k8 k^> , k1, k2, k3, k4, k5, k6, k7, k8 on the single-chain domain can be encoded as 2 8 =256 cases, when k1, k2, k3, k4 are (0, 1, 1, 1, 1, 1, 0), the XOR function is realized; when k1, k2, k3, k4 are (0, 1, 1, 0, 1, 0, 0, 1), the full adder summation (full subtractor difference) function is realized; Based on the above method for constructing a logic operation module, any n-input-one-output logic operation module can be constructed according to circuit requirements.
5. The method for constructing a power addition logic circuit based on DNA domain coding according to claim 1, characterized in that: In the step 4, a DNA circuit for obtaining a four-digit square root is constructed using a domain coding logic operation module, and four typical input values 0, 1, 4, and 9 are calculated. The DNA circuit for obtaining a four-digit square root constructed by the domain coding logic operation module consists of four logic NOT gates, three three-input logic AND gates, one two-input logic OR gate, and one two-input logic AND gate. Corresponding to the concept of the above-mentioned domain coding logic operation module, one-input, two-input, and three-input logic operation modules are used to implement it. First, the input signals A0, A1, A2, and A3 are inverted through the logic NOT gate to obtain Then use 3 domain encoding fan-out gates to input chain A0, Perform fan-out operation to obtain signal chains with the same logic value. The encoding structures of input chains A0, A1, A2, and A3 are<i1L^b i1R^T^m1L^a m1R^> ,<i2L^b i2R^T^m2L^am2R^> ,<i3L^bi3R^T^m3L^am3R^> ,<i3L^bi3R^T^m4L^am4R^> , all represent logical value 0. The specific reaction process of the 4 input chains being inverted through the logic NOT gate is as follows: A0+NA0→sp94+sp91(22) A1+NA1→sp89+sp90(23) A2+NA2→sp87+sp88(24) A3+NA3→sp85+sp86(25) Reaction formulas (22)-(25) use a one-input one-output logic operation module to implement the reaction process of inverting the logic value of input chain A0. In reaction formula (22), after input chain A0 is paired with double-stranded NA0, single-stranded sp94 is generated, which is encoded as<m1L^am1R^T^u1L^bu1R^> and waste sp91, the logic value of the detached single-stranded sp94 is opposite to the logic value of the input chain A0, representing a logic value of 1; the reaction process of reaction formulas (23)-(25) is similar to reaction formula (22), and single-stranded sp89 is produced, which is encoded as<m2L^am2R^T^u2L^bu2R^> , sp87 is encoded as<m3L^am3R^T^u3L^bu3R^> and sp85 is encoded as<m4L^am4R^T^u4L^bu4R^> , which is opposite to the logic value of input chain A1, A2, and A3, and all represent logic value 1. The fan-out operation is performed on the input chain A0 using three domain coded fan-out gates. The specific reaction process is as follows: A0+IFA0→sp93+sp94(26) A0+IFA1→sp92+sp94(27) A1+NA1→sp89+sp90(28) sp89+NFA10→sp82+sp83(29) sp89+NFA11→sp81+sp83(30) A2+NA2→sp87+sp88(31) sp87+NFA20→sp79+sp80(32) sp87+NFA21→sp78+sp80(33) Reaction formulas (26)-(27) respectively fan out two single chains sp92 and sp93 with the same logic value as A0, both representing logic value 0; reaction formula (28) reverses the logic value of A1 single chain representing logic value 0 to obtain sp89 single chain representing logic value 1. In reaction formulas (29)-(30), sp89 single chain reacts with fan-out gate double chains NFA10 and NFA11 respectively, fanning out two single chains sp81 and sp82 with the same logic value. The structure of sp81 single chain is<u2L^b u2R^T^b2L^b b2R^> , representing a logical value of 1, and the single-chain structure of sp82 is<u2L^b u2R^T^b1L^b b1R^> , representing the logical value 1. Reaction (31) inverts the logic value of the A2 single chain representing the logic value 0 to obtain the sp87 single chain representing the logic value 1. In reactions (32)-(33), the sp87 single chain reacts with the fan-out gate double chains NFA20 and NFA21 respectively, fanning out two single chains sp78 and sp79 with the same logic value. The structure of the sp78 single chain is<u3L^b u3R^T^b4L^b b4R^> , representing a logical value of 1, and the single-chain structure of sp82 is<u3L^b u3R^T^b3L^b b3R^> , representing the logical value 1. Secondly, two three-input one-output logic AND gate modules, one two-input one-output logic OR gate and one two-input one-output logic AND gate are used to implement AND operation and realize the logic value output of Y1. The specific reaction process of the two three-input one-output logic AND gate modules is as follows: In reaction formula (34), after the input chain A2 and the inverted input chains A0 and A3 react with the double-stranded chain F6 of the three-input and one-output module, the double-stranded structure of F6 is {T^*}[u4L^b u4R^T^]:[m3L^am3R^T^]:[u1 L^b u1R^T^]<c1L^a c1R^> , producing single-stranded sp60 and waste, the generated sp60 single-stranded<u1L^b u1R^T^c1L^a c1R^> ; In reaction formula (35), input chains A0, A3 and input chain After the double-stranded F11 of the three-input and one-output module reacts, single-stranded sp60 and waste are produced. The double-stranded structure of F11 is {T^*}[m4L^a m4R^T^]:[b3L^b b3R^T^]:[a1 L^aa1R^T^]<c2L^a c2R^> The resulting sp64 single chain is<a1L^a a1R^T^c2L^ac2R^> . The single-chain sp60 and sp64 obtained after the operation of the two logic and modules enter the two-input and one-output logic or gate module for logic or operation. The specific reaction process is as follows: sp60+H1→sp55+waste(36) sp64+sp55→sp49+waste(37) H1 in reaction (36) is a double chain of two-input and one-output logic OR gates, and its encoding structure is {T^*}[c1 L^a c1R^T^]:[c2L^a c2R^T^]<d1L^a d1R^> , with single-chain sp60<u1L^b u1 R^T^c1L^a c1R^> After strand displacement, sp55 single strand is formed; in reaction equation (37), sp55 and sp64 single strand<a1L^a a1 R^T^c2L^a c2R^> After strand displacement, a single-stranded sp49 is obtained, and the strand structure of sp49 is<c2L^a c2R^T^d1L^a d1R^> . After the operation of the logic OR gate module, the generated single-chain sp49 and the single-chain sp82 of the input chain enter the two-input and one-output logic AND gate module for further AND operation. The specific reaction process is as follows: sp49+H6→sp46+waste(38) sp46+sp82→sp43+waste(39) H6 in reaction (38) is a double chain of two-input and one-output logic AND gates, and its encoding structure is {T^*}[d1 L^a d1R^T^]:[b1L^b b1R^T^]<d2L^a d2R^> , after reacting with single-stranded sp49, a double-stranded sp46 output and waste are obtained; in reaction formula (39), the double-stranded sp46 reacts with the single-stranded sp82 to produce a single-stranded sp43, and its encoding structure is<b1L^b b1 R^T^d2L^a d2R^> . The sp43 single chain obtained after the above logic operation reaction output is further amplified through the amplification gate. The specific amplification reaction process is as follows: sp43+amp11→sp41+sp42(40) In reaction formula (40), amp11 is a double chain of the amplification gate, and its structure is {T^*}[d2L^a d2R^T^]<pL^a pR^> After passing through the amplification gate, a single chain of sp41 and waste sp42 are generated. The single chain structure of sp41 is<d2L^a d2R^T^pL^a pR^> . In order to more conveniently observe the output logic value, the single-chain sp41 is output in the form of a fluorescent chain, which is realized through the fluorescent reporting gate Report. The specific reaction process is as follows: sp41+ReportL11→OUTL11+sp39(41) ReportL11 in reaction formula (41) is the double chain of the fluorescent gate, and its structure is {T^*}[pL^apR^] <fluor01>After passing through the fluorescent reporter gate, the single-stranded OUTL11 and the waste sp39 are generated. The single-stranded structure of OUTL11 is [pL^a pR^] <fluor01> , the output fluorescent chain logical value represents 0. Finally, a three-input and one-output logic AND gate module is used to realize the logic value output of Y0. The reaction process is as follows: sp78+B7→sp68+sp69(42) sp69+sp81→sp63+sp62(43) sp63+sp92→sp56+sp57(44) In reaction (42), B7 is a domain-encoded double chain of a three-input and one-output AND gate, and its structure is {T^*}[b4L^b b4R^T^]:[b2L^b b2R^T^]:[a2L^a a2R^T^]<c3L^a c3R^> , after the sp78 single strand and the B7 double strand undergo strand displacement, a sp69 double strand mixture and waste sp68 are produced; in reaction formula (43), after the sp69 double strand mixture and the sp81 single strand undergo strand displacement, waste sp62 and a double strand mixture sp63 are produced; in reaction formula (44), after the double strand mixture sp63 and the sp92 single strand undergo strand displacement, a sp56 single strand and a sp57 double strand mixture are produced, wherein sp56 is the desired single strand output, and its strand structure is<a2L^aa2R^T^c3L^a c3R^> . The single-stranded sp56 continues to be amplified through the amplification gate, and then output in the form of a fluorescent chain through the fluorescence reporter gate. The specific reaction process is as follows: sp56+amp21→sp51+sp52(45) sp51+ReportL21→sp47+OUTL21(46) In reaction formula (45), amp21 is a double-stranded amplification gate, and its structure can be set as {T^*}[c3L^ac3R^T^]<zL^a zR^> , after chain displacement with single-stranded sp56, sp51 single-stranded and sp52 double-stranded waste are generated. The chain structure of sp51 is<c3L^ac3R^T^zL^azR^> In reaction equation (46), after the strand displacement between sp51 and the fluorescent reporter gate ReportL21, double-stranded waste sp47 and fluorescent chain OUTL21 are generated. The chain structure of OUTL21 is<zL^a zR^fluor11> . Compared with the four-digit square root circuit designed with a dual-track circuit, when the initial parameters of the species are set to be consistent, the initial reactants of the four-digit square root circuit designed with domain coding are reduced from 130 to 61, and the reaction time is reduced to 1 / 24 of that of the dual-track circuit. The circuit construction is simpler and the output results are more stable.
6. The method for constructing a power addition logic circuit based on DNA domain coding according to claim 1, characterized in that: The method of the power addition numerator circuit in step five is: obtaining the truth table of the power addition operation logic circuit through logical relations, and constructing the power addition logic circuit according to the truth table. The power addition logic circuit is mainly composed of 4 NOT gates, 13 AND gates, and 5 OR gates. The output expression of the power addition logic circuit is: Y4=X3X2X1X0.
7. The method for constructing a power addition logic circuit based on DNA domain coding according to claim 1, characterized in that: In step 5, the domain coding logic operation module and the power addition logic circuit are used to construct a power addition numerator circuit to implement the addition operation of 2x and 2x (x is 0-3), for example, 20 and 2 3 The addition operation. The power addition numerator operation circuit is composed of 4 NOT gates composed of one-input and one-output modules, 5 AND gate modules with three-input and one-output, 8 AND gate modules with two-input and one-output, 5 OR gate modules with two-input and one-output, 7 fan-out gates and 5 fluorescence reporting gates. Suppose the domain encoding molecular chain of input chains X0, X1, X2, and X3 is <a0^1a1 ^ T^b0^0b1 ^ >, <a2 ^ 1a3 ^ T ^ b2^0b3^>,<a4^1a5^T^b4^0b5^> , <a6 ^ 1a7 ^ T ^ b6 ^ 0b7 ^ >, representing the logic value 0000; after inverting the input chain X0, X1, X2, and X3 through the NOT gate, the input chain with the opposite logic value can be obtained A fan-out gate fans out a single chain with the same logical value.
8. The method for constructing a logic operation module according to claim 1 further comprises constructing an AND gate, an OR gate logic operation module, a fan-out gate, and a fluorescence reporter gate molecular circuit, and obtaining an output fluorescence chain OUTL01() after DNA chain replacement.<m1^0m2^fluor01> Represents logical value 0, OUTL12()=<n1^1n2^fluor12> Represents logical value 1, OUTL21()=<p1^0p2^fluor21> Represents logical value 0, OUTL31()=<q1^0q2^fluor31> Represents logical value 0, OUTL41()=<w1^0w2^fluor41> Represents logical value 0.
