84 results about "Macromolecular 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 relates to a drug target virtual screening method based on interactive fingerprints and machine learning. According to the method, based on traditional molecular docking, the interactive fingerprints of known active and non-active micromolecules and target protein are trained through machine learning to obtain a screening model of targets, and the obtained model is used for virtual screening. The specific targets are specifically trained, the specificity of each kind of targets is fully considered, and the defect of insufficient fitting of a traditional scoring function is avoided; interaction energy of each micromolecule and each residue in a binding pocket is calculated, so that effective binding sites or binding modes can be found; non-linear fitting is carried out through machine learning, and compared with linear fitting, the correlation or coupling effect between all the interaction energy can be better processed; by means of the method, enrichment of active molecules is better promoted.

The invention discloses a protein-ligand interaction fingerprint spectrum-based drug target prediction method. The method comprises the steps of collecting a large amount of diversified target and ligand complex crystal structures; building a reference protein-ligand interaction fingerprint spectrum model; predicting a possible combination mode of a to-be-tested drug and each target by molecular docking; building a drug and target interaction fingerprint spectrum model; and calculating the similarity between a fingerprint spectrum and the reference interaction fingerprint spectrum model, and the affinities of the drug and targets, sorting the targets of a target library by integrating docking scoring, the fingerprint spectrum similarity and the affinities, and outputting a potential target of the drug. According to the method, drug and target interaction modes are sorted and predicted by adopting an interaction fingerprint spectrum method, so that the shortcoming of relatively low success rate of predicting the drug and target interaction modes due to the molecular docking is overcome; and the targets are sorted by adopting a comprehensive index Cvalue, and the advantages of various methods are brought into play, so that the prediction accuracy of the drug target is radically improved.

The invention relates to a virtual screening method for a novel cancer-preventing or anti-cancer medicament by taking Keap1 as a target point. The method comprises the following steps of: 1) determining a PDB structural data of a Keap1 protein structure; 2) determining an active center according to an active cysteine residue site of the Keap1 by adopting molecular docking software, and setting active bags; 3) screening small molecule ligand; 4) establishing a small molecule ligand database for docking; 5) docking the small molecule ligand in the small molecule ligand database for docking and the active bags one to one according to the set active bags by using the molecular docking software; and 6) primarily determining a pilot medicament with chemical cancer-preventing or anti-cancer effect according to the sequencing of the docking results. The method can obtain a clue of an active compound in short time, and then screens the cancer-preventing or anti-cancer medicament by using animal horizontal screening or high-pass molecule platform screening so as to greatly improve the speed and the efficiency and shorten the research period of a new medicament.

The present invention relates to the field of drug screening, and specifically relates to a method for detecting binding specificity between a ligand and a target and a drug screening method. The detection method includes: molecular docking through the ligand and the target, obtaining an energy spectrum of the ligand, introducing the ratio of intrinsic specificity, and thus determining the binding specificity between the ligand and the target. The detection method compared with conventional methods has the advantages of good specificity, high accuracy, fast speed and low cost. The invention provides a new detection method for structure-based virtual drug screening. Based on the detection method, a method of two-dimensional virtual drug screening directed at affinity and specificity is developed. At the same time, the detection method provides a new description characteristic for the side effect research of small molecule compounds, and provides guidance for chemical modification and transform of drug lead compounds. Relative to conventional mere affinity-concerning virtual drug screening, the specificity dimension is added to the method, so the chances of discovery of drug lead compounds are greatly improved.

The invention relates to the field of medicine, and discloses a high-throughput screening method for active polypeptides based on tandem mass spectrometry and molecular docking. The invention uses modern biochemical technology to extract and prepare mixed polypeptides from marine molluscs, fish and other animals. After preliminary activity separation, the active site/component group is determined, and the amino acid sequence of all polypeptides in the active site/component group is identified by LC-MS/MS method. In the molecular docking software, all polypeptide sequences are homologously modeled, and then imported Molecular docking software docks with the target protein, analyzes the binding rate of the polypeptide and the target protein, and evaluates its inhibitory/activating activity, and screens the confirmed active polypeptide through solid-phase synthesis combined with in vitro activity evaluation to verify the accuracy of the screening. The invention has the advantages of fast and efficient search for marine active polypeptides, strong operability and important application value.

The invention discloses collagen-integrin alpha2beta1 interacted polypeptide inhibitors and a screening method thereof. The collagen-integrin alpha2beta1 interacted polypeptide inhibitors provided for the first time are LWWNSYY, LRWNSPY and LYWNSGY. According to a molecular mechanics-Poisson-Boltzmann solvent accessible surface area analysis method, the interaction between collagen short peptide and integrin alpha2beta1 on the surface of blood platelet is analyzed, so as to obtain a key residue with affinity interaction; therefore, a collagen-integrin alpha2beta1 interacted polypeptide inhibitor library can be constructed, the polypeptide inhibitors having high affinity to collagen can be obtained by screening polypeptides through molecular docking, root mean square deviation comparison and molecular dynamic simulation. Isothermal titration calorimetry experiments and blood platelet adsorption experiments proved that the obtained polypeptide inhibitors can inhibit the bonding between the collagen and integrin alpha2beta1, thus being potential high-efficiency thrombus inhibitors.

The invention discloses a metabolite-peptide-aptamer rapid screening method based on the molecular docking simulating computation technology. The metabolite-peptide-aptamer rapid screening method includes the steps that (1) a target metabolite is determined; (2) a potential polypeptide library is obtained, wherein binding force exists between the potential polypeptide library and the target metabolite; (3) the potential polypeptide library and the target metabolite are subjected to molecular docking forecasting. The metabolite-peptide-aptamer rapid screening method is high in speed and wide intarget range, a large quantity of manpower and material resources are not required, harm to experimenter bodies is avoided, and limiting factors of wide application of current peptide aptamer are avoided. According to the metabolite-peptide-aptamer rapid screening method based on the molecular docking simulating computation technology, the peptide-aptamer screening procedure can be simplified, the library capacity is increased to a greatest degree, the metabolite peptide aptamer with the suitable specificity and affinity is thus conveniently screened out, and the metabolite-peptide-aptamer rapid screening method is used for designing such as kit and sensor detection, and is applied to detection of the field such as nutriology, biology and clinical diagnosis.

The invention provides a method for screening a chitinase OfChtI inhibitor. The method comprises the steps that firstly, according to a pesticide-similar performance rule, micromolecular compounds which accord with the condition are screened out from an SPECS library, and a first database is established; a three-dimensional structure of OfChtI and a ligand eutectic crystal is acquired from a Protein Data Bank, compared and analyzed, and an active pocket is determined; then, according to mutual application and analysis, a pharmacophore model based on a receptor is established, the first database is screened, and a second database is established; then, by using a molecular docking program, micromolecular compounds in the second database are docked and graded, and a third database is established; finally, by using a framework analysis model in software, compounds in the third database are subjected to framework classification, and the chitinase OfChtI inhibitor with the structure is obtained, wherein the structure is shown in the formula (I). Through research, it is indicated that the chitinase OfChtI inhibitor has good inhibitory activity on chitinase OfChtI.

The invention discloses a novel affinity peptide ligand of murine polyoma capsomere as well as a designing and screening method thereof. Based on a compound of natural existing capsomere and a minor capsid structure protein VP2-C, a bionic designing process of the affinity peptide ligand of the capsomere is constructed. The method comprises the following steps: firstly, resolving intermolecular interactions in the compound by utilizing a molecular dynamics simulation combined Poisson-Boltzmann solvent accessible surface area (MM/PBSA) method; determining a hot spot residue ligand of the VP2-C and a simplified affinity model of the hot spot residue ligand so as to construct an affinity peptide ligand bank of the capsomere; screening the high-affinity peptide ligands in manners of molecular docking and molecular dynamics simulation by virtue of the MM/PBSA method. The affinity chromatography experiment proves that the obtained affinity peptide ligand DWDLRLLY which ranks the first during the screening process can be used for effectively separating and purifying the capsomere by one step from an escherichia coli cracking supernatant, thereby having wide application prospect in preparation of virus-like particles.

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 relates to a method for virtually screening cholesterol degrading medicine with 24-dehydrocholesterol reductase (DHCR24) being a target point. The method includes the steps that 1, the molecular structure of DHCR24 is determined; 2, molecular docking software is adopted, the active center of macromolecular docking of the medicine is determined according to a combined pocket which is formed after desmosterol and DHCR24 are docked, and an active pocket is set; 3, a macromolecular ligand databse used for docking is arranged; 4, according to the set active pocket, by the utilization of the molecular docking software, macromolecular ligands in the macromolecular ligand database used for docking and the active pocket are docked in sequence; 5, results which are screened after primary docking are accurately docked, and the candidate medicine having the effect of cholesterol degrading are determined. By the adoption of the method, within short time, the macromolecular candidate medicine which has the effect of competitive restraining of DHCR24 and is developed into the novel cholesterol degrading medicine is obtained, in this way, the research and development efficiency is greatly improved, and the research period of new medicine is shortened.

The present invention relates to the development of a virtual screening model for predicting antipsychotic activity using quantitative structure activity relationship (QSAR), molecular docking, oral bioavailability, ADME and Toxicity studies. The present invention also relates to the development of QSAR model using forward stepwise method of multiple linear regression with leave-one-out validation approach. QSAR model showed activity-descriptors relationship correlating measure (r²) 0.87 (87%) and predictive accuracy of 81% (rCV²=0.81). The present invention specifically showed strong binding affinity of the untested (unknown) novel compounds against anti-psychotic targets viz., Dopamine D2 and Serotonin (5HT_2A) receptors through molecular docking approach. Theoretical results were in accord with the in vitro and in vivo experimental data. The present invention further showed compliance of Lipinski's rule of five for oral bioavailability and toxicity risk assessment for all the active Yohimbine derivatives. Therefore, use of developed virtual screening model will definitely facilitate the screening of more effective antipsychotic leads/drugs with improved antipsychotic activity and also reduced the drug discovery cost and duration.

The invention aims to establish an efficient, fast and reliable screening method of TTR (transthyretin) small-molecule inhibitors, overcomes the defects of the prior art and is applicable to design of medicines for amyloidosis caused by TTR fibrosis. A small-molecule database is screened and predicted by means of 3D-QSAR (3-dimensional quantitative structure activity relationship), molecular docking, pharmacophore models and the like; small molecules capable of serving as lead compounds are determined preliminarily; further cell screening is performed. The screening method is fast and efficient; a plurality of drug screening and design methods based on receptors and ligands are applied; accordingly, reliability of screening results is improved greatly. Cell levels are subjected to biological screening by lead compounds obtained by screening, so that screening speed is higher and development and search cycle of novel inhibitors is shortened.

The invention discloses a method for simultaneously realizing docking by multiple molecules, and belongs to the technical field of medicine screening. The multiple molecules simultaneously realize docking for making preparation for parallel computing; through parallel computing, the simultaneous docking on a plurality of pairs of molecules can be performed; Hadoop is used as a parallel computing framework; a corresponding cluster is built according to the Hadoop and is used for molecular docking; each pair of molecules requiring the docking are respectively stored onto different computers; each pair of separated molecules are subjected to molecular docking; and docking results in different equipment are summarized. The simultaneous docking on multiple molecules can be realized; the Hadoopis used as the parallel computing framework; the simultaneous docking of the multiple molecules is realized; the operation is simple; and the huge computing cost can be reduced.

The invention discloses a structure prediction method of a voltage-gating sodium ion channel, and particularly relates to a structure modeling method of constructing the eukaryotic voltage-gating sodium ion channel Nav1.5 pore structural domain open state based on a template. The method includes the steps that a rosetta membrane protein homology modeling method is used for obtaining a germ sodium ion channel template of a crystal tripolar structure, and four subunit structures of the Nav1.5 pore structural domain are constructed and composed preliminarily; sorting is carried out according to the grading condition of all construction models, the structure with the maximum score is selected as the initial structure of all the structural domains; the four constructed subunit structures are compared to four 4CBC subunits, and the assembled overall structure is optimized; based on structure data and test data of existing local anesthetics drugs, molecular docking is carried out on the optimized structures, screening and evaluating strategies are set according to the existing experiment data to determine the reliability of model construction.

The invention belongs to the technical field of pharmaceutical molecular biology, and in particular relates to application of mycobacterium tuberculosis gene Rv3290c used for screening an antituberculous inhibitor target. The gene is characterized in that the nucleotide sequence of the gene is shown in the sequence table SEQ. ID NO:1, and the sequence of protein coded with the gene is shown in the SEQ. ID NO:2. Through a virtual screening method, aiming at activity center of a natural substratge of Rv3290c, 20 small molecular compounds with high affinity to the combining sites of the natural substratge of Rv3290c are screened from a small molecular compound database by operating a molecular docking program, so that a bacteriostatic compound (benzothiophene compound 14#) is obtained. The compound is named ethyl-2-[(3, 5-dibromo-2, 4-dihydroxyl benzyl) amino]-4,5,6,7-tetrahuydro-benzothiophene-3-carboxylic acid. The bacteriostatic effect of the compound in mycobacterium tuberculosis is evaluated.

The invention belongs to the technical field of agricultural biotechnologies, and relates to establishment of a cotton bollworm sterol carrier protein 2 (SCP-2) small-molecule inhibitor virtual screening method. The method comprises the following steps: according to structural data of cotton bollworm sterol carrier protein 2 (SCP-2), analyzing a key amino acid residue so as to confirm a binding pocket; screening, scoring and calculating binding free energy by using molecular docking software; performing structure clustering and visual analysis on an obtained compound, thereby obtaining a small-molecule inhibitor for SCP-2 protein. The small-molecule inhibitor can be applied to screening, study and development of novel environmental-friendly pesticides for multiple agricultural pests of lepidoptera as the main target.