171 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 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 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 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 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 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.