167 results about "Molecule docking" patented technology

The invention searches the novel micromolecule inhibitor pyrazolo (1, 5-a) miazines compounds of cyclin-dependent kinase CDK9 (cyclin-dependent kinase) through the virtual screening of a computer, biometrically measures activity thereof, and validates interaction mechanism. The invention specifically comprises the following steps: the three-dimensional crystal conformation of the cyclin-dependent kinase family member CDK9 is obtained in a way of homology modeling; and micromolecule three-dimensional database is screened with DOCK (molecular docking). The invention uses a MTT tumor cell growth inhibition test to biometrically measures the activity of the selected compounds, researches the selected compounds pyrazolo (1, 5-a) miazines with high activety in a way of molecular mechanism, validates the inhibiting effect of the compounds to the activity of CDK9 kinase, and clarifies the interaction mechanism of the compounds for inhibiting the external activity and the molecule of various malignancies such as lung cancer, osteosarcoma, oophoroma, cervical carcinoma, breast cancer, etc.

The invention discloses a method for predicting the binding free energy of protein and ligand based on a progressive neural network, and belongs to the technical field of computer-aided drug design. The method comprises the steps: obtaining a pdb file from a PDBbind database, establishing local database, acquiring an amino acid molecule within 4.5 angstroms in the protein binding pocket by takingthe ligand molecule as a center, performing extended connectivity fingerprint calculation, carrying out SPLIF fingerprint calculation, searching for the number of salt bridges and hydrogen bonds between protein and ligand molecules, converting the structural information of the protein and the ligand into a one-dimensional tensor, and establishing a training set, a verification set and a test set;training the progressive neural network by using the training set; optimizing and searching hyper-parameters for prediction; through comparison with a molecular docking result, obtaining a higher Pearson correlation coefficient. According to the invention, the technical problem of how to convert a three-dimensional structure of protein and ligand molecules into tensors which are easy to calculateby a computer and input the tensors into the progressive neural network for training and optimization is solved, and the calculation rate and the prediction accuracy are greatly improved.

The invention provides a screening method of a farnesyl pyrophosphate synthase (FPPS) inhibitor. The screening method comprises the following steps: (1) constructing an FPPS template; (2) preparing a data set; 3) performing virtual screening based on molecular docking; 4) performing virtual screening based on the pharmacophore model; 5) calculating binding energy; 6) integrating the docking scores in the steps 3), 4) and 5), the pharmacophore model FitValue value and the binding energy to obtain the FPPS inhibitor; and 7) carrying out FPPS enzyme activity inhibition experiment on the FPPS inhibitor obtained by virtual screening, and determining the FPPS inhibitor with the structure shown in the formula I. The method gives full play to the advantages of theoretical screening, reduces the blindness of drug synthesis, effectively improves the hit rate of positive drugs, saves manpower, material resources and financial resources, and realizes the new use value of old drugs. The invention further provides application of the FPPS inhibitor obtained through screening in preparation of drugs for treating colon cancer.

The invention discloses a virtual screening method for anti-inflammation and anti-rejection drugs taking CRAC channels as targets. The virtual screening method comprises the following steps that (1), CRAC channel protein structural data are obtained to construct a homology model; (2), an active center is determined, and an activity bag is set; (3), according to the activity bag, molecular docking software is utilized for carrying out docking marking on compounds; (4), the compounds with the CRAC channel blocking activity are determined preliminarily; (5), activity screening is carried out on the compounds, and leading drugs with the CRAC channel blocking activity are obtained; (6), a pharmacophore model is constructed, the small-molecule compounds on which molecule docking is not carried out or the small-molecule compounds on which docking is carried out are matched and compared for guiding screening of the compounds or structure optimizing of the leading compounds. According to the virtual screening method for the drugs, the number of the compounds on which activity testing is carried out is reduced, the cost is saved, the screening efficiency is improved, and the virtual screening method can be used for further developing the novel anti-inflammation and anti-rejection drugs.

The invention provides a method, a system and a device for establishing a traditional Chinese medicine action mechanism model based on network pharmacology. The method comprises the following steps: acquiring gene targets corresponding to various components of the traditional Chinese medicine; acquiring a target gene target; taking an intersection of the gene targets corresponding to the components of the traditional Chinese medicine and the target gene targets to obtain a gene set; constructing a protein interaction network for the gene set; analyzing nodes in the protein interaction networkto obtain key gene nodes; performing GO analysis and KEGG analysis on the key gene nodes for further gene screening; in the screening result, conducting molecular docking on the traditional Chinese medicine components and protein corresponding to the core gene, verifying the binding capacity, and obtaining the target traditional Chinese medicine components. According to the scheme, efficient drugcomponent analysis can be assisted, the analysis process is simplified, the complexity of an analysis algorithm is reduced, convenience and rapidness are achieved, and the accuracy is high.

The invention discloses an epitope polypeptide combination capable of inducing immunity and application thereof, belongs to the technical field of biology, and aims to carry out molecular design of related vaccines by utilizing immunoinformatics on the basis of epitope analysis optimization. Based on a structural antigen epitope vaccine design strategy, a B cell epitope, a Th epitope and a CTL epitope on a new coronavirus S protein are determined through immunoinformatics to induce a main neutralizing antibody, activate cellular immune response and induce body fluid and cellular immune balance. The epitope vaccine is designed through connection of a molecular adjuvant and candidate antigen epitopes, antigenicity, physicochemical properties, protein secondary structure and tertiary structure modeling of the epitope vaccine are analyzed, vaccine conformation B cell epitopes are analyzed by means of a structural biological tool, and immune response characteristics of the vaccine are verified through molecular docking with TLR4 and immune response simulation stimulation. Information analysis results show that the designed candidate epitope combination has well balanced humoral immune and cellular immune response capabilities.

The invention discloses an amine transaminase AcATA mutant and application of the amine transaminase AcATA mutant in preparation of a sitagliptin intermediate. The amine transaminase AcATA mutant is obtained by single mutation at the 122th site of an amino acid sequence shown in SEQ ID No.2. The amino acid sequence of the amine transaminase AcATA mutant is shown in SEQ ID No.2. The amino acid sequence of the amine transaminase AcATA mutant is shown in the description, wherein methionine at the 122 position is mutated into histidine, valine or phenylalanine. According to the invention, sites possibly influencing the catalytic activity are obtained through molecular docking, homologous modeling and other methods, and site-specific mutagenesis is carried out, so that the finally obtained aminotransferase AcATA mutant has high enzyme activity, and the enzyme activity is higher than 460U/g and is more than 4 times of that of a wild type; the catalyst can efficiently catalyze the sitagliptin intermediate precursor ketone 1-piperidine-4-(2, 4, 5-trifluorophenyl)-1, 3-dibutanone to synthesize the sitagliptin intermediate (R)-3-amino-1-piperidine-4-(2, 4, 5-trifluorophenyl)-1-butanone, and the 24-hour conversion rate is up to 90%.

The invention relates to a super-large-scale marine natural product molecular docking method based on a heterogeneous many-core architecture, and belongs to the technical field of drug screening, and the method comprises the following steps: constructing a multi-layer parallel scheduling framework based on a heterogeneous supercomputing platform, and designing a molecular docking process of master-slave core asynchronous parallel computing, the invention provides a data access optimization scheme of a molecular docking key algorithm. According to the method, data reading, task scheduling and parallel computing in the molecular docking process are optimized from the aspect of nuclear memory access, the super-large-scale parallel drug virtual screening process is achieved, the computing speed is increased, and meanwhile the drug screening precision is improved. The I/O pressure of the system is reduced, the advantages of the heterogeneous many-core architecture are fully played, and the overall performance of the virtual drug screening system is improved.

The invention discloses a target screening method for coronavirus pneumonia resistance of sophora flower bud tea, and belongs to the technical field of medicines. The method comprises the following steps: screening active components and predicting a target; preparing a molecular docking ligand and a receptor; carrying out component target molecular docking to screen active components; predicting adisease target; constructing a compound-target-disease network; and carrying out key target function enrichment analysis. According to the research, a network pharmacology method and a molecular docking technology are adopted to explore active ingredients and potential targets of sophora flower buds for COVID-19, molecular docking verification is carried out, a component-target network is constructed, and the sophora flower bud tea is compared with lianhua Qingwen capsules and golden flower Qinggan particles to explore a mechanism action channel, and an idea is provided for subsequent basic experiments.

The invention discloses an application of Bevantol screened based on molecular docking and molecular dynamics simulation as an AIBP inhibitor, and the Bevantol screened based on simulation is used forinhibiting the interaction between AIBP and apoA-I, so cholesterol is inhibited from flowing out of cells. The invention also provides a simulation screening method for Bevantol screened based on molecular docking and molecular dynamics simulation as the AIBP inhibitor. The method comprises the following steps: obtaining an AIBP protein structure through homologous simulation, downloading a smallmolecular structure data set for docking, and performing a molecular docking process and molecular dynamics simulation in a ZINC database. According to the invention, the AIBP structure is obtained through homologous simulation, the virtual screening of FDA authenticated drugs is performed through molecular docking and molecular dynamics simulation on the basis of the new thought of old drugs, and it is found that Bevantol can be stably bonded to a bonding interface of AIBP and apoA-I. Or, cholesterol can be inhibited from flowing out of cells, and a new application of Bevantol is excavated.

The invention discloses a construction method of a heparin C5 isomerase high-catalytic-activity strain, and belongs to the technical field of bioengineering. The method comprises the following steps:firstly, selecting Escherichia coli as host bacteria, then carrying out expression optimization on C5 isomerase by utilizing a way of fusing a solubilizing label at an N end, and further carrying outprotein engineering modification on an optimized C5 protein sequence through molecular docking so as to obtain a high-activity production strain. According to the invention, microbial cells are used for expressing the C5 obtained after mutation of 106 amino acids from valine to arginine for the first time, the catalytic activity of the obtained enzyme is 5.81 U/mL and is improved by 141% comparedwith that before mutation, and the specific enzyme activity is 145.14 U/mg and is improved by 128% compared with that before mutation.

The invention belongs to the technical field of drug molecules and particularly relates to an application of mycobacterium tuberculosis gene Rv0233 in screening an antituberculous inhibitor target. The gene is characterized in that a nucleotide sequence of the gene is as shown in a sequence table: sequencer (SEQ) ID NO: 1, and a coded protein sequence of the gene is as shown in the sequence table: sequencer (SEQ) ID NO: 2. Eighteen small molecule compounds which have a high affinity with a binding site of natural substrate of Rv0233 screened out from a small molecular compound database through a molecular docking program aiming at an active centre of the natural substrate of the Rv0233 by the way of virtual screening. One bacteriostatic compound (pyrazole compound 51#) is obtained. The name of the compound is 2-({[1-(4-methyl pheny)-H-pyrazol-4-y1] methyl} amino) ethanol. The target gene evaluates the bacteriostatic effect of the compound on the mycobacterium tuberculosis.

The invention discloses a 17 beta-hydroxysteroid hydroxylase 3 mutant enzyme, a coding gene and engineering bacteria. The 17 beta-hydroxysteroid hydroxylase 3 mutant enzyme is abbreviated as 17 beta-HSD3<G186R/Y195W>, and an amino acid sequence of the 17 beta-hydroxysteroid hydroxylase 3 mutant enzyme is as shown in SEQ ID NO.1. 17 beta-hydroxysteroid hydroxylase 3 is subjected to molecular modification by adopting a rational design technology, the 17 beta-hydroxysteroid hydroxylase 3 mutant enzyme with improved affinity with a substrate is obtained through methods of homologous modeling, molecular docking, binding energy calculation and the like, the enzyme activity is improved by 1.66 times as compared with the original enzyme activity, and by utilizing the strategy, the catalytic activity of the 17 beta-hydroxysteroid hydroxylase 3 can be obviously improved. The 17 beta-hydroxysteroid hydroxylase 3 mutant enzyme is coded, so that the yield of testosterone is up to 3.95 g/L, and technical support and data reference are provided for large-scale biological preparation of the testosterone which is a male hormone drug.

The invention provides a virtual drug screening method and device based on molecular docking. The method comprises the following steps: inputting drug molecular information; converting the drug molecule information into n-dimensional floating point type data information; outputting the information of each atom of the drug molecule according to the n-dimensional floating point type data informationby adopting an LSTM network, and summarizing the information of each atom to obtain a vector representing the characteristics of the drug molecule; assigning a weight to the vector representing the characteristics of the drug molecule through an attention network to obtain a vector model of the drug molecule; and screening the activity of the drug molecules according to the vector model. According to the scheme, the AUC value can be increased by 2%, and higher robustness is achieved.

The invention provides a lead compound for a targeted human FKBP51 protein and a screening method and application thereof, belonging to the technical field of biochemical pharmacy. According to the lead compound and the screening method and application thereof, an FK1 structural domain of FKBP51 is used as a receptor; FK506 of the FKBP51 is selected to be combined with a sack; molecular docking is performed by using a Glide program; 150 small molecular compounds are obtained by virtual screening from more than 1.5 million of compounds and are used for fluorescence quenching experiments; according to the experiments, a combination action of the compounds and the FK1 is verified, and the binding property of a target protein and compounds with a strong docking effect is researched; two kinds of cells LNCaP and DU145 are selected to verify the cell viability of screened small molecular compounds resisting prostate cancer; meanwhile, the structural biology research on a compound formed by the FKBP51 and small molecular lead compounds is performed. According to the lead compound provided by the invention, a cell model and a mouse model of CRPC (Castration Resistant Prostate Cancer) are established, the effectiveness of the lead compound to the CRPC is evaluated, and an action mechanism and a rule of the lead compound and the target protein are explained at the molecular level; a foundation is provided for researching and developing new drugs for treating common prostate cancer and the CRPC.

The invention provides design and construction of AuEH2G218S and AuEH2S247Y mutant enzymes with high enantio-selectivity. The mutation sites are finally determined by sequence homology analysis, homologous modeling, molecular docking and dynamic simulation. Mutant genes obtained by a megaprimer RPC technology are named Aueh2G218S and Aueh2S247Y. The invention further discloses a method for construction and efficient expression of mutant engineering bacteria; and the prepared mutant enzymes have the characteristics of high enantio-selectivity and catalytic activity, and have relatively large industrial production potential.

The invention discloses a mutant bacterium nitroreductase gene and an application thereof and belongs to the field of enzyme engineering. On the basis of protein three-dimensional structures and molecular docking, phenylalanine in the 124 position of Escherichia coli nitroreductase NfsB interacts with side chain groups of a multi-nitro substrate, so that positioning of the substrate in an activity pocket is affected. Mutants F124W, N71S/F124W, F123A/F124W and N71S/F123A/F124W can catalyze the specificity of a prodrug CB1954 for treating cancers to produce a 4-NHOH product with high biotoxicity. Meanwhile, the catalytic activity of the mutants is improved by 7-24 times when being compared with that of wild type enzymes, and the N71S/F123A/F124W is the most significant. The nitroreductase mutants with specific reduction selectivity have the good application prospect in aspects of treatment of cancers and other diseases.

The invention relates to a molecular docking result screening method based on positive compound residue contribution similarity, and belongs to the technical field of drug screening, and the method comprises the steps of constructing a positive compound library, optimizing target spots and compound structures, and optimizing a docking result screening method. According to the method disclosed by the invention, the screening probability of active compounds is increased in the process of finding potential patent medicine compounds, so that the precision of the screening method is fundamentally improved, the accuracy of screening the potential patent medicine compounds is improved, and the calculation cost and the time cost are greatly saved.

The invention provides an application of Irinotecan based on molecular docking and molecular dynamics simulation screening as an AIBP inhibitor, and the Irinotecan is used for inhibiting interaction between AIBP and apoA-I, so that cholesterol is inhibited from flowing out of cells. The invention also provides a method for Irinotecan as an AIBP inhibitor based on molecular docking and molecular dynamics simulation screening. The method comprises the following steps: obtaining an AIBP protein structure through homologous simulation, and downloading a small molecular structure data set for docking, a molecular docking process and molecular dynamics simulation in a ZINC database. According to the method, the structure of AIBP is obtained through homologous simulation, the virtual screening isconducted on FDA authenticated drugs through molecular docking and molecular dynamics simulation on the basis of the new thought of old drugs, and it is found that Irinotecan can be stably bonded toa bonding interface of AIBP and apoA-I; or cholesterol can be inhibited from flowing out of cells, and the new application of the Irinotecan is excavated.

A method of discovering a drug candidate, comprising: a step in which a computer device uses bioinformatics to determine a disorder-to-order transition region of a target protein; a step in which the computer device performs molecular docking on the disorder-to-order transition region in conjunction with a library of specific compounds to select first candidate compounds capable of binding to the disorder-to-order transition region from among the compound library; and a step in which the computer device performs a molecular dynamics simulation for the first candidate compounds and the disorder-to-order transition region to select a second candidate compound from among the first candidate compounds.

The invention provides a small-molecule inhibitor taking human hexokinase 2 as a target spot and application of the small-molecule inhibitor, and belongs to the technical field of pharmacy. According to the invention, hexokinase 2 is used as a receptor, an inhibitor binding pocket of hexokinase 2 is selected, molecular docking is carried out by using a Glide program, virtual screening is carried out from more than 1,600,000 compounds to obtain the small-molecule inhibitor LY2019-001 of targeting human hexokinase 2, and enzyme activity inhibition experiments and MTT cell proliferation inhibition experiments are carried out; and the inhibition effect of the compound LY2019-001 on hexokinase 2 and the growth inhibition effect of the compound LY2019-001 on cervical cancer cells HeLa, liver cancer cells HepG2 and lung cancer cells A549 are verified. The found small molecules and pharmaceutical salts thereof can provide a basis for new drug research and development for treating diseases related to hexokinase 2, such as liver cancer, lung cancer, endometrial cancer, breast cancer, ovarian cancer, pancreatic cancer or prostate cancer. The structure of the lead compound can be further optimized, and the lead compound has a relatively good application prospect.

The invention discloses application of tripterine in preparation of anti-coronavirus products, and belongs to application in the field of medicines. The inhibition effect of the tripterine on the S protein and ACE2 protein of novel coronavirus COVID-19 is proved by adopting a molecular docking technology, the affinity experiment determines that the tripterine has relatively strong affinity with the S protein, and the tripterine has an obvious inhibition effect on the coronavirus in a cell experiment within a range of 5-40 mu M and has concentration dependence. The tripterine is a specific inhibitor of coronavirus and has specific novelty. The tripterine can be used for preparing the products for inhibiting the coronavirus and has wide practicability.

The invention provides a screening method of heterologous competitive antigens for improving immunodetection sensitivity, which comprises the following steps: performing corresponding molecular descriptor calculation on enrofloxacin analogues, and performing principal component analysis on the molecular descriptors to obtain a principal component analysis result; respectively measuring to obtain the semi-inhibitory concentration of the enrofloxacin and the semi-inhibitory concentration of each enrofloxacin analogue, and further calculating to obtain the cross reaction rate of each enrofloxacin analogue; according to the principal component analysis result and the corresponding cross reaction rate of each enrofloxacin analogue, establishing a mathematical model and carrying out classified learning to obtain a classified learning result; and according to a classification learning result, carrying out molecular docking by utilizing a quinolone molecular crossover and lysine to obtain a conformation, and carrying out configuration optimization to obtain a minimum-energy conformation so as to determine the optimal heterologous competitive antigen. The invention is convenient for screening and determining the heterologous competitive antigen capable of improving the immunodetection sensitivity, and has a good application prospect.

The invention provides a molecular conformation searching method based on a hybrid fireworks algorithm. The molecular conformation searching method is characterized by comprising the following steps of: S1, setting a docking area of receptor molecules, and expressing the docking area by using a docking box which is used for storing ligand conformations; S2, initializing a plurality of initial fireworks, wherein each firework represents a ligand conformation, expressing the ligand conformations as solution vectors, and setting a receptor-ligand binding affinity scoring function as a fitness function; S3, constructing a solution space according to the solution vectors, wherein the solution space comprises a plurality of layers; S4, constructing an operator of a fireworks algorithm; and S5, constructing the hybrid fireworks algorithm by combining the fireworks algorithm and a local search algorithm, and searching for an approximately optimal ligand conformation in the docking box by usingthe hybrid fireworks algorithm. According to the invention, the average time for docking on a test compound in molecular docking is reduced, and a molecular docking speed is increased; and meanwhile,the approximate optimal value of the fitness function can be found, and the precision of molecular docking is improved.

The invention discloses a molecular docking method based on a polarizable bond model. The method is characterized in that on the basis of traditional molecular docking, polarizable bonds contained inthe ligands are recognized according to a protein environment where ligands are located and charges are updated; then molecular docking is conducted again (the updated charges are forcibly used); andthe operation is repeated till energy is converged, and the optimal binding mode is obtained. Compared with the prior art, the method has the advantages that the polarization effect of EPB charges isenhanced, the intermolecular hydrogen bond interaction is enhanced, the molecular docking precision is effectively improved; and the method is more efficient than a QM/MM equivalent molecular dockingmethod.