80 results about "Conformational change" patented technology

The invention discloses a deep learning prediction method fused with multi-modal features, which can accurately identify protein hidden binding sites in a ligand-free (apoo) state. The method comprises the following steps of: firstly, constructing a protein graph by taking residues as nodes and taking C alpha distance less than or equal to 14 as edges, wherein node feature sets comprise amino acid one-hot, secondary structures, atomic attributes, protein language model embedding and BLOSUM62 evolutionary information, and edge features comprise distance and angle similarity; then capturing three-dimensional geometric equivariant features by adopting an equivariant graph neural network (EGNN), and modeling a chemical topological relation by using a graph isomorphic network (GINE) with edge features; eGNN and GINE double-branch feature fusion and global dependence integration are realized through gating cross attention and gating multi-head attention; and finally, inputting the fusion features into a Kolmogorov-Arnold network (KAN) classifier, and predicting whether each residue belongs to a hidden binding site or not. The method can adapt to large-scale conformation change without coordinate alignment, AUC and F1 on a standard data set are remarkably superior to those of an existing method, high robustness and generalization are kept for multi-chain protein and complex conformation, and the method can be widely applied to drug target discovery and structure-driven drug design.

The invention relates to the technical field of gene editing, in particular to a Cas9 protein mutant and application thereof. According to the present invention, the mutation is introduced at the position far away from the catalytic site to induce the Cas9 protein conformation change so as to obtain the new Cas9 protein mutant, only the Cas9-sgRNA target chain is cut, and the Cas9-sgRNA non-target chain is not cut, such that the new Cas9 protein mutant can be used for constructing the novel base editor, and the high-efficiency base editing can be performed on the mammalian cell genome. The Cas9 protein mutant disclosed by the invention is fused with a mutant TX with DNA binding deletion of 3 '-> 5' exonuclease TREX2, so that the gene editing efficiency of a 3'terminal generated by paired single-nick enzyme cutting can be greatly improved, and the safety of the Cas9 protein mutant is maintained.

The invention provides a method for analyzing interaction between procambarus clarkia arginine kinase and shark source nano antibody. The method comprises the following steps: performing three-dimensional structure prediction on a VNAR sequence, and screening a high-confidence VNAR model by using a Laplace map; docking an amino acid sequence corresponding to the VNAR model with an arginine kinase sequence to obtain an optimal compound model, and analyzing an interaction site of an arginine kinase epitope region and a nanometer antibody complementary determining region CDR3; performing molecular dynamics simulation on the compound model, calculating conformational change indexes and binding free energy through energy optimization, system balance and extended simulation sampling, and outputting a binding stability sequence of the nano antibody and arginine kinase; the method comprises the following steps: screening out a high-stability nano antibody, pre-incubating a fusion protein of the high-stability nano antibody and immobilized arginine kinase to form a compound, adding serum of an allergic patient for competitive binding, quantifying the binding activity of residual IgE through an immunodetection technology, and verifying the inhibition effect of the shark source nano antibody on the sensitization effect of arginine kinase.

The embodiment of the invention discloses a virus three-dimensional reconstruction method and system based on three-dimensional Gaussian splashing. The method comprises the following steps: acquiring three-dimensional point cloud data including a target virus; performing molecular dynamics simulation on the target virus based on a coarse graining molecular dynamics model, identifying a high-energy interaction region, and obtaining binding energy data of the target virus and a host molecule in an interaction process; tracing the conformation change of the virus structure to obtain conformation change data; performing three-dimensional Gaussian splashing processing on the point cloud data to generate an in-situ visual three-dimensional model of the target virus; wherein in the Gaussian splashing processing, the shape, the direction and the weight of a Gaussian kernel are dynamically adjusted according to combined energy data and conformation change data. According to the method and the device, efficient virus three-dimensional model generation is realized aiming at virus characteristics.

The invention discloses a preparation method and application of an electrochemical biosensor for dynamically monitoring Cyt c in tumor cells based on fast scanning voltammetry. The preparation method is characterized by comprising the following steps: 1) preparing a PtNE nano electrode; (2) preparing the PtNE / Apt nano electrochemical biosensor; and (3) accurately puncturing the PtNE / Apt electrode into cytoplasm of a single Hela cell through a three-dimensional micro-control system, so that Apt and intracellular Cyt c are specifically combined and subjected to conformational change, and 3 '-end modified Fc is close to the surface of the electrode, thereby generating a remarkable electrochemical signal. The change of Fc redox peak current is dynamically monitored through fast scanning voltammetry, the quantitative relation between the Cyt c concentration and the peak current is established, and the relation between the Cyt c concentration and the cell activity is monitored according to the quantitative relation. The device has the advantages of high sensitivity, excellent anti-interference capability and remarkable signal amplification effect.

The invention discloses a non-competitive detection method based on aptamer allosteric activation CRISPR / Cas and application, and belongs to the technical field of biosensing. The detection method solves the problems that in a CRISPR / Cas detection system based on the nucleic acid aptamer in a competitive mode, the design requirement for partial complementary chains of the nucleic acid aptamer is high, and multiple requirements of low background signals, efficient target recognition and effective activation of the CRISPR / Cas system are difficult to consider. According to the detection method, the conformational change in the process that the aptamer recognizes the target is converted into the dynamic difference of the footrest-mediated strand displacement reaction, and the cascade footrest-mediated strand displacement reaction is designed to activate the CRISPR / Cas system. The detection method realizes high-sensitivity, simple, convenient and rapid ATP detection, and is applied to freshness evaluation of pork, beef and mutton.

Disclosed are systems, methods, and computer software for determining a conformational change in a structure of a protein. One method includes delivering a magnetic nanoparticle-nanobody (MNP-NB) complex to a sample containing a protein, where the MNP-NB complex will bind to the protein in the sample. An external magnetic field is applied to the sample with a magnetic field generation system. Signals are detected from the MNP-NB complex that reflect a response to the external magnetic field and a conformational change in a structure of the protein in the sample is determined from the signals.

According to the method for detecting the conductance of the protein molecules and the application of the method, asymmetric modification is carried out on the tunneling electrode pair and the protein molecules, so that the protein molecules can enter a tunneling area in a fixed posture and form asymmetric single-molecule junctions with the tunneling electrode pair, the activity of the protein molecules can be kept to the maximum extent, and the conductivity of the protein molecules is detected. Therefore, the device capable of stably detecting the conductance of the protein molecules for a long time can be constructed and obtained, and the device can be used for researching the dynamic conformation of the protein, screening small-molecule drugs targeting the protein molecules and analyzing the interaction relationship between the small-molecule drugs and the protein molecules. The tunneling electrode device and the real-time electrical measurement technology are used for achieving protein detection on the single molecule level, the conformation change process of protein such as biological enzyme and the action characteristics of the protein and small molecules are comprehensively described on the high time resolution scale, and the design and optimization efficiency and success rate of existing drugs are expected to be improved.

Disclosed are protein switches, components of such protein switches, and uses thereof, which can sequester biologically active peptides and / or binding domains, keeping them in an inactive ("off") state until combined with a second, designed polypeptide, termed a key, thereby inducing a conformational change that activates ("on") the biologically active peptide or binding domain.

The invention discloses a cell membrane in-situ drug membrane protein target screening method based on variable configuration DNA, and belongs to the technical field of biological medicine. Two pairs of functionalized nucleic acid structures are constructed, the first pair is S1S2 semi-complementary DNA double strands, the second pair is S3S4 DNA-RNA hybrid double strands, and the S1S2 structure is covalently coupled to a non-natural amino acid site-directed modified membrane protein through a click chemical reaction in a living cell to realize tagging of the membrane protein; when the candidate drug coupled in S3 interacts with the membrane protein, triggering an allosteric response system to release the tagged chain in S1; the released DNA tag is subjected to PCR amplification and sequencing, and accurate identification and analysis of a membrane protein target are realized according to a tag sequence. The invention provides a high-specificity and non-in-vitro drug membrane protein target screening technology. According to the technology, active compound discovery or accurate screening of drug membrane protein targets in a living cell in-situ environment can be realized.

The invention relates to an antibody-biomacromolecule conjugate. The antibody-biomacromolecule conjugate comprises an antibody targeting module, a complement effect module and a connexon, the antibody targeting module can be specifically combined with a cell membrane surface antigen, and the complement effect module is a key enzyme C1s in a classical complement pathway or a functional structural domain with complement splitting activity of the key enzyme C1s. The linker is used for connecting the antibody targeting module with the complement effect module, and is designed to generate cutting or conformational change on the outer side of a cell membrane or in an extracellular microenvironment, so that the complement effect module is converted from a limited state to a functional accessible state; to promote initiation of a classical complement pathway in the neighborhood of the cell membrane located by the antibody targeting module. The antibody-biomacromolecule conjugate provided by the invention can be used for engineering regulation and control of complement-related reactions.

The application discloses a VEGF / TIE-2 double-targeting polypeptide and application thereof in preparation of an antitumor drug, and relates to the technical field of biological medicine.The VEGF / TIE-2 double-targeting polypeptide (named as RTP) provided by the application is composed of an amino acid sequence capable of target-recognizing VEGF and TIE-2, an amino acid sequence capable of self-assembling to form a beta-sheet nanofiber, an amino acid sequence capable of target-recognizing carbonic anhydrase IX and an enzyme-reactive amino acid sequence capable of being specifically cut by MMP-2.RTP can occur conformational change and self-assemble in tumor cells to form stable water-insoluble nanofibers, and can strongly inhibit tumor neovascularization and metastasis through the VEGF and TIE-2 double-signal pathways and inhibit the progress of the tumor.

The present invention discloses a molecular dynamics simulation analysis method for ultrasonic perturbation of the Piezo1 protein, belonging to the field of ultrasonic perturbation. In the molecular dynamics simulation, ultrasonic perturbation is achieved by applying an ultrasonic function to the boundary, and successful ultrasonic loading is verified based on the water density on the X-axis. Furthermore, an analytical method is established to explain the effects of ultrasound on cell membranes from multiple angles, such as cell membrane thickness and lipid-protein interactions, and further study the effects of cell membranes on proteins, thereby determining the effects of ultrasound on the Piezo1 structure. This invention is the first to use ultrasonic loading coarse-grained molecular dynamics simulation to study the conformational changes of the Piezo1 mechanosensitive ion channel, providing important research ideas for future applications in ultrasound therapy, acoustic genetics, and other fields.

The present invention provides a method for detecting the electrical conductivity of protein molecules and its application. By asymmetrically modifying a tunneling electrode pair and a protein molecule, the protein molecule can enter the tunneling region in a fixed posture and form an asymmetric single-molecule junction with the tunneling electrode pair, which can maximize the activity of the protein molecule. This constructs a device that can stably detect the electrical conductivity of protein molecules over a long period of time. The device can be used for dynamic conformational studies of the protein itself, screening of small molecule drugs targeting the protein molecule, and analysis of the interaction between small molecule drugs and protein molecules. The present invention utilizes tunneling electrode devices and real-time electrical measurement technology to achieve protein detection at the single-molecule level, comprehensively depicting the conformational change process of proteins such as biological enzymes and their interaction characteristics with small molecules on a high time resolution scale, and is expected to improve the efficiency and success rate of existing drug design and optimization.

The invention discloses a neutralizing antibody with an AQP3 channel blocking function as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The neutralizing antibody can be specifically combined with an extracellular domain of AQP3, after combination, a water channel and a small molecule transport function of the AQP3 are blocked through steric hindrance and conformation change, and meanwhile, antigen combination specificity is reserved. The preparation method is realized through'recombinant antigen-immunization-B cell screening culture-recombinant antibody expression and affinity purification-ELISA detection ', and the functions of the antibody are ensured. The antibody can be efficiently combined with AQP3 positive cells, is strong in targeting property and high in specificity (the serum titer reaches 1: 1024 * 10, and the purified antibody titer is greater than or equal to 1: 128 * 10), and can be independently used or combined with a nano-carrier for treating related diseases, so that the technical bottleneck that a common AQP3 antibody can only be combined and cannot efficiently play a blocking role is solved.

The invention discloses a method for detecting the conformational change of an APO-Cascade protein. Through mutation of Cas8 protein amino acid N376 and Cas5 protein K169 in a Casade protein, the obtained Cas8 and Cas5 labeled by non-natural amino acids can maintain functions, and at the same time, the mutant type of the Cas5 / 8 protein can be subjected to fixed-point fluorescence labeling; according to the method, the Cas6 is used as a template, the N end of the Cas6 is further modified with biotin, and a formed Casade compound can be fixed on a biotin-PEG functionalized single-molecule slide, so that the conformation state of the Casade protein can be truly reflected by using single-molecule fluorescence resonance energy transfer, an effective means is provided for in-vitro research on the structure-function relationship of a system in CRISPR / Casade, and the method has a wide application prospect. And the method is of great significance in designing the Cascade protein with optimized properties and enabling the Cascade protein to play new functions.

The invention belongs to the technical field of medicine and pharmacy, and particularly relates to application of an AP1B1 allosteric activator of ethyl gallate. In the invention, AP1B1 is a beta 1 subunit (AP1B1) of a linking factor associated protein complex 1 (AP-1), and is an essential component for assembling a functional AP-1B complex. The ethyl gallate is used as an allosteric activator of AP1B1 and is specifically combined with an allosteric pocket of the AP1B1 to induce the AP1B1 to generate conformational change, so that the vesicle transportation function of an AP1B complex is activated, and the substrate-side membrane protein sorting capacity is recovered. A target dependence experiment verifies that the effect of ethyl gallate on promoting tight junction protein ZO-1 expression and membrane localization in AP1B1 knocked-down Caco-2 cells is remarkably weakened, and it is prompted that the intestinal barrier protection function of ethyl gallate depends on AP1B1. The invention provides a new strategy for developing medicines for treating intestinal barrier injury related diseases.

This invention discloses a neutralizing antibody against influenza A virus and its applications. The neutralizing antibody has a heavy chain and a light chain. The heavy chain comprises heavy chain CDR1 (amino acid sequence as shown in SEQ ID NO:5), heavy chain CDR2 (amino acid sequence as shown in SEQ ID NO:6), and heavy chain CDR3 (amino acid sequence as shown in SEQ ID NO:7); the light chain comprises light chain CDR1 (amino acid sequence as shown in SEQ ID NO:8), light chain CDR2 (amino acid sequence as shown in SEQ ID NO:9), and light chain CDR3 (amino acid sequence as shown in SEQ ID NO:10). The antibody of this invention exhibits highly efficient and broad-spectrum neutralizing activity against influenza A virus, and can bind to multiple subtypes of hemagglutinin, inhibiting the cleavage of hemagglutinin precursor proteins and conformational changes of hemagglutinin in acidic environments. This invention has significant implications and promising applications for the prevention and treatment of diseases caused by influenza A virus.

Disclosed herein are sensor chips, imaging systems, and methods of preparing and using the same. The sensor chips disclosed herein include a substrate and a plurality of nanoplasmon rulers immobilized on the substrate. Each nanoplasmon ruler includes a first plasmonic element and a second plasmonic element connected by opposing ends of a single strand nucleic acid connector. Binding of an analyte to the single strand nucleic acid connector induces a conformational change in the single strand nucleic acid connector. The conformational change modulates an end-to-end distance between the first plasmonic element and the second plasmonic element, thereby modulating the nanoplasmonic coupling between the first plasmonic element and the second plasmonic element.

The invention discloses a cell single-molecule mechanical force sensor for single-molecule mechanical force detection in a cell phagocytosis process as well as a preparation method and application of the cell single-molecule mechanical force sensor. The sensor comprises a microsphere substrate and a plurality of double-stranded DNA mechanical probes modified on the surface of the microsphere substrate, the probe is composed of a first single-stranded DNA and a partially complementary second single-stranded DNA and forms an FRET or fluorescence quenching pair, when a pulling force applied to the probe by a receptor-ligand effect exceeds a preset melting threshold value in a process of swallowing or wrapping microspheres by a cell, the double-stranded DNA generates melting or conformational change and generates fluorescence signal change, and the fluorescence signal change is detected by the first single-stranded DNA and the partially complementary second single-stranded DNA. Therefore, the detection of the monomolecular mechanical force of the phagocytic interface is realized. By adjusting the geometric conformation and sequence design of the probe, a probe library with different melting force thresholds can be constructed, and quantitative analysis and spatial distribution characterization of mechanical force in the phagocytosis process are realized. According to the application, a three-dimensional phagocytic interface can be truly simulated, and an effective tool is provided for revealing a mechanism for regulating and controlling endothelial cell phagocytic behaviors through blood flow mechanics and screening related disease drugs.

The invention provides a method for detecting mycotoxin by using a carbon nanotube field effect transistor biosensor based on nucleic acid conformation change, which comprises the following steps: anchoring a modified nucleic acid aptamer on the surface of an ion shielding gold film layer through a gold-sulfur bond by using a CNT-FET biosensor with an ion shielding gold film layer above a channel to construct a sensing interface; the modified nucleic acid aptamer consists of a target mycotoxin original nucleic acid aptamer sequence and an oligomeric thymine deoxynucleotide fragment directionally inserted into the 5'end of the target mycotoxin original nucleic acid aptamer sequence; during detection, mycotoxin in a to-be-detected sample is specifically combined with the modified nucleic acid aptamer, secondary conformation change of the mycotoxin close to the gold film layer is triggered, the CNT-FET biosensor converts an electric field effect caused by conformation displacement into a channel carrier concentration change signal, and quantitative detection is achieved according to the linear relation between the signal and the mycotoxin concentration. According to the method, the nucleic acid aptamer is directionally modified, so that the electrical response after the low-charge-quantity / electrically neutral mycotoxin is combined with the sensor is enhanced, and the detection sensitivity is greatly improved.

The present invention discloses a porous silicon deoxyribozyme fluorescent probe and its application in evaluating the anticancer activity of traditional Chinese medicine. The fluorescent probe comprises amino-modified porous silica nanoparticles, fluorescent molecules loaded in the nanoparticle pores, and DNA hairpins HP1 and HP2 covalently linked to the nanoparticle surface. The HP1 sequence contains a complementary sequence to the microRNA to be detected, and the HP2 sequence contains a zinc ion-specific deoxyribozyme cleavage site. After HP1 binds to the microRNA, the root is opened, the HP1 loop undergoes a conformational change, and binds to the HP2 loop nucleotide sequence. With the assistance of zinc ions, the zinc ion-specific deoxyribozyme is activated, which then cuts HP2 at the cleavage site, releasing the fluorescent molecules in the nanoparticle pores. The microRNA is detected based on the intensity of the fluorescent molecules. The probe can specifically and sensitively detect trace amounts of microRNA in a system.

This invention discloses a machine learning-enhanced fluorescence detection method for silver nanoclusters containing split nucleic acid aptamers, used for the detection of adenosine triphosphate (ATP) in aquatic products, belonging to the field of analytical chemistry. This detection method uses two split nucleic acid aptamers of ATP as templates to synthesize DNA-AgNCs. In the presence of the target ATP, a conformational change is induced, resulting in a decrease in fluorescence intensity. Quantitative analysis of ATP is achieved by detecting this fluorescence change. To further improve the detection effect, machine learning is introduced to preprocess the fluorescence spectrum. A recursive feature elimination algorithm is used to screen characteristic wavelengths, and a multi-dimensional feature set is constructed using maximum fluorescence intensity, peak area, and full width at half maximum (FWHM). The optimal classification model is obtained through cross-validation optimization. This invention combines aptamer recognition, DNA-AgNCs, and machine learning to construct a detection method where fluorescence dynamically decreases with increasing ATP concentration. It has advantages such as low cost, simple operation, and good biocompatibility, effectively improving detection sensitivity and stability, and has promising application prospects in the qualitative and quantitative analysis of ATP in aquatic products.

The invention relates to a voltage-gated anion channel protein designed from de novo and application of the voltage-gated anion channel protein. The voltage-gated anion channel protein (dVGACs) designed from the beginning has a funnel-shaped pentamer structure, each monomer in the pentamer is composed of three transmembrane helixes, and the amino acid sequence of each monomer comprises SEQ ID No. 1 or a mutant thereof, at least one amino acid of the 43rd, 47th, 51th and 55th sites of the amino acid sequence of the mutant is mutated into arginine or aspartic acid. The dVGACs provided by the invention have selectivity to chloride ions, have voltage-responsive conformational change, and cause opening of a central pore channel at a membrane potential of about + 40 mV or + 20 mV and above. Due to the properties, the biosensor has a wide application prospect in the aspects of neurological disease treatment, cell behavior regulation and control, biosensor development and the like.

The invention provides a flexible manifold space generation molecular docking method and device based on interactive representation, and the method comprises the steps: obtaining a protein coordinate and a small molecule coordinate according to a sampling state; on the basis of a pre-trained interaction representation learning model, generating protein-molecule interaction representation according to the noisy protein pocket and the noisy ligand small molecule; based on a pre-trained generation model, generating a denoised state according to the protein coordinates, the small molecule coordinates and the protein-molecule interaction representation; and obtaining a binding conformation of the protein pocket and the ligand micromolecule according to the denoised state. According to the method, interactive representation containing atomic-scale distance information between protein and small molecules is used as a generation condition of a translation and rotation dihedral angle of the ligand small molecules and a dihedral angle of a protein pocket side chain, and conformational changes of the ligand small molecules and the protein pocket side chain are generated in a flexible manifold space; the rapid and accurate butt joint of the protein pocket and the ligand small molecule is realized.

The embodiment of the invention generally relates to the technical field of bioengineering, in particular to a nucleotide construct, an adeno-associated virus vector, and a system and a method for detecting neural activity. The nucleotide construct comprises an open reading frame, and the open reading frame comprises a voltage response domain coding sequence and a sound wave modulation domain coding sequence. The nucleotide construct is configured to be expressed on an astrocyte membrane under the control of a promoter so as to provide a recombinant protein with a voltage response domain and an acoustic wave modulation domain, so that the recombinant protein can generate corresponding reversible conformation change in response to membrane potential change of the astrocyte, the acoustic characteristics of the recombinant protein can be changed by the reversible conformation change. In this way, the recombinant protein can sense changes in membrane potential and modulate the reflection characteristics to ultrasonic waves.

The invention provides a probe system and method for detecting AKI-related miRNA based on primer exchange reaction and G-quadruplex, and belongs to the technical field of molecular probe fluorescence sensing. Target miRNA-driven PER amplification, PER product-induced G tetramer conformational change and G-Quadruplex-ThT signal'lightening 'mechanism are organically combined to detect the AKI-related miRNA. A low-background label-free signal amplification system is constructed for accurate detection of target miRNA, has the characteristics of high sensitivity, strong specificity, simplicity in operation and the like, and still keeps good performance in an actual sample. Besides, by designing the dumbbell-shaped hairpin probe HP, specific detection of different targets can be realized, and the establishment of the technical platform provides a new method for research and development of a kit for simultaneously realizing rapid detection of disease biomarkers such as small molecules, nucleic acid, protein and the like.

The invention provides a complex enzyme design method and system based on conformational change transition state search and application. The method comprises the following steps: determining a complex enzyme and one or more known steady-state structures of the complex enzyme; searching a transition state of the conformation change of the complex enzyme according to the steady state structure; determining an activity factor influencing the activity of the complex enzyme based on the structure information and the energy information of the transition state; designing one or more enzyme mutants according to the active factors, analyzing the effect of the enzyme mutants and verifying whether the enzyme mutants are qualified or not; and taking the enzyme mutant which is verified to be qualified as the designed complex enzyme. Complex enzyme activity and specificity design is carried out by applying conformational change transition state search, and conformational change dynamics mechanism details directly related to the activity of complex enzyme are accurately and rapidly obtained, so that comprehensive and rational design of the activity and specificity of complex enzyme becomes possible; therefore, site-directed mutagenesis can be carried out on the gene, and the total cost of research and development of complex enzyme products is greatly reduced.

The invention discloses an enzyme functionalized sensor for detecting nano plastic DPV in a biological matrix as well as a preparation method and a detection method of the enzyme functionalized sensor, and belongs to the field of nano plastic detection. The sensor comprises an electrode and CAT enzyme, wherein the surface of the electrode is modified with positively charged nano-gold particles, and the CAT enzyme is fixed through positive and negative electrostatic interaction. According to the sensor, the CAT enzyme and the nano plastic are combined to generate conformational change to change the activity of the CAT enzyme so as to cause DPV signal change, the sensitivity is high, the sensor has similar DPV signal response to different types of nano plastic, and a unified calibration model can be utilized to detect a complex biological matrix system so as to realize total amount determination of various nano plastic. And the electrochemical detection method does not need complex instruments and pretreatment, and provides a rapid, economic and extensible detection scheme for nano plastic exposure evaluation and environmental monitoring.

Described herein are compositions and methods for bioluminescent analyte detection. In some embodiments, a recombinant bioluminescent polypeptide sensor is disclosed comprising a luminescent signaling domain, an analyte binding domain, and one or more peptide linkers, wherein the luminescent signaling domain is oriented in relation to the analyte binding domain such that binding of an analyte to the analyte binding domain induces a conformational change in the luminescent signaling domain to generate a luminescent signal.