74 results about "Binding pocket" patented technology

The invention relates to the technical field of computer-aided drug design, in particular to a drug molecule screening and optimizing method based on artificial intelligence prediction, which comprises the following steps: S1, obtaining a dynamic protein conformation set and molecular multi-dimensional characterization: obtaining a dynamic conformation set of a target protein and a physicochemical property spatial distribution diagram of a binding pocket of the dynamic conformation set, a two-dimensional molecular map topological structure and three-dimensional conformation coordinates of the drug molecules are obtained; s2, multi-modal fusion prediction is carried out; s3, generating interpretable optimization guidance; and S4, automatic iterative optimization: performing batch prediction and screening on the new candidate molecular structure, taking the screened optimal molecule as a new starting point, repeatedly executing the interpretability optimization guidance generation step and the step until an iteration termination condition is met, and outputting a final optimized molecule list. Through the multi-modal fusion deep learning model, the interaction strength of the drug molecules and the target protein can be quickly and accurately predicted, and the screening efficiency of the drug molecules is greatly improved.

The invention belongs to the field of medical technology analysis, and discloses an analysis method and system for revealing a hidden binding pocket of a drug target, and the method comprises the steps: firstly obtaining a representative conformation metastable state of a target protein through conventional molecular dynamics simulation and clustering analysis; secondly, constructing a Markov state model to analyze a dynamic transformation rule between conformations; carrying out enhanced sampling by adopting meta-dynamics, and deeply exploring a rare conformation space; and finally, constructing a free energy landscape to quantitatively evaluate the relative stability of the conformation, and identifying a hidden binding pocket in the stable rare conformation. According to the method, the limitation of a single calculation means is overcome, a full-chain calculation system of dynamic conformation analysis-hidden cavity feature mining-novel ligand rational design is constructed, and the formation mechanism and potential druggability of the hidden pocket can be comprehensively revealed from the two dimensions of dynamics and thermodynamics; and an efficient and accurate calculation framework is provided for research and development of innovative drugs targeting difficult drug targets.

The invention relates to application of a DDX39B protein inhibitor in preparation of acute leukemia treatment medicines, and belongs to the technical field of biological medicines. In order to solve the problems of single acute leukemia treatment scheme and lack of novel medicines at present, the invention provides application of a DDX39B protein inhibitor in preparation of acute leukemia treatment medicines. Targeted inhibition of DDX39B can significantly hinder proliferation of leukemia cells, promote apoptosis and differentiation of cells, retard the process of cell cycles, delay disease progression in vivo and prolong the lifetime of model animals. On the basis of an RNA (Ribonucleic Acid) binding pocket structure of DDX39B, through high-throughput drug screening, the small molecule compound HMU-4051C is firstly identified as a DDX39B targeted inhibitor to effectively kill leukemia cells, and a new application of the DDX39B protein inhibitor in preparation of acute leukemia treatment drugs is developed.

The invention belongs to the technical field of biological enzyme engineering, and particularly relates to a glucosamine-6-phosphate synthetase mutant and application thereof. A plurality of glucosamine-6-phosphate synthase mutants capable of remarkably improving the yield of N-acetylglucosamine are screened by performing single-point mutation or combined mutation on amino acid residues near a substrate binding pocket of the glucosamine-6-phosphate synthase or on the surface of protein of the glucosamine-6-phosphate synthase. According to the technical scheme, a foundation is laid for producing glucosamine by further transforming escherichia coli through metabolic engineering.

The application belongs to the technical field of bio-chemical industry, and particularly relates to a P450 enzyme mutant and application of an engineering bacterium thereof in synthesis of calcifediol, the mutant is one or more point positions in an amino acid sequence based on a wild type P450 enzyme Vdh being mutated; the amino acid sequence of the wild type P450 enzyme Vdh corresponds to GenBank accession number CP069288.1. Through systematic molecular dynamics simulation, conservation analysis and substrate binding pocket engineering on the Vdh enzyme, multiple key mutation sites are successfully screened and obtained. The constructed combined mutant (such as I114R / N173M / Q310R, Vdh-M3) shows extremely high hydroxylation activity, and the pure enzyme activity can reach 9.8 times of the wild type enzyme, greatly improving the conversion rate from vitamin D3 to calcifediol.

The invention discloses a sulfonylurea structure-containing compound as well as a preparation method and application thereof, and relates to the technical field of preparation and application of medical inhibitor compounds. The structure of the compound containing the sulfonylurea structure is shown in the specification. The preparation method comprises the following three steps: synthesizing an intermediate 1 from raw materials through Suzuki coupling reaction, obtaining an intermediate 2 through Sonogashira coupling reaction, and synthesizing a target compound through Williamson reaction. Through the synergistic effect of sulfonyl and ureido, accurate recognition and efficient embedding of a kinase ATP binding pocket are achieved, and the technical bottlenecks that a traditional c-Met inhibitor is poor in selectivity, drug resistance is likely to be generated and the synthesis process is complex are solved.

This invention relates to an antibacterial membrane-penetrating peptide and its applications. The amino acid sequence of the antibacterial membrane-penetrating peptide includes the sequence shown in SEQ ID NO.1 or a sequence with more than 70% homology to the sequence shown in SEQ ID NO.1. This invention screened and obtained a short peptide that specifically binds to the bacterial Hsp70s protein. It was found that this peptide binds to the Hsp70s protein through a traditional substrate-binding pocket, exhibiting an unusually high affinity for the protein in the DnaK-ATP state. The short peptide can inhibit Hsp70s protein activity to a certain extent, preventing it from aiding in the renaturation of denatured luciferase. Furthermore, while maintaining the integrity of the bacterial cell membrane, this short peptide has a superior ability to cross the bacterial cell membrane. The invention further discusses its application potential in the preparation of antibacterial drugs and antibiotic adjuvants, providing new ideas for solving current problems such as bacterial resistance and the difficulty in discovering new antibiotics.

The application discloses a drug design method and device based on topological data analysis, equipment and medium, relates to the technical field of computer-aided drug design, and the method comprises the steps of obtaining a plurality of three-dimensional structure conformations of a target protein, determining the binding pocket region of each three-dimensional structure conformation, and constructing a conformation set; calculating a topological descriptor representing the topological relationship between atoms based on the atomic coordinates of the binding pocket region of each three-dimensional structure conformation, and converting the topological descriptor into a corresponding conformation feature vector; performing a pooling operation on the conformation feature vector corresponding to each three-dimensional structure conformation to generate a unified topological feature representation representing the common topological feature mode of the target protein binding pocket under a plurality of three-dimensional structure conformations; and screening or generating candidate drugs based on the unified topological feature representation. The common topological invariant information of a plurality of conformations is used to represent the flexible protein binding pocket, the screening omission caused by single conformation representation is reduced, and the representation accuracy and the calculation efficiency are considered.

The invention belongs to the technical field of biochemical engineering, and particularly relates to application of a P450 enzyme mutant and engineering bacteria thereof in synthesis of calcifediol, and the mutant is obtained by mutating one or more sites in an amino acid sequence based on a wild type P450 enzyme Vdh; the amino acid sequence of the wild type P450 enzyme Vdh corresponds to the accession number of GenBank, namely CP069288.1. Through systematic molecular dynamics simulation, conservative analysis and substrate binding pocket engineering on the Vdh enzyme, a plurality of key mutation sites are successfully screened and obtained. The constructed combined mutant (such as I144R / N173M / Q310R, Vdh-M3) shows extremely high hydroxylation activity, the pure enzyme activity of the combined mutant can reach 9.8 times that of a wild type enzyme, and the conversion rate from vitamin D3 to calcifediol is greatly increased.

The invention belongs to the technical field of molecular biology and drug screening, and provides a screening method of capsaicin targeting SOCS5-RBMX protein interaction and application of the capsaicin, an SOCS5-RBMX protein complex structure is analyzed, and SOCS5-RBMX binding structural domains and SOCS5-RBMX binding key sites are determined; the effect of inhibiting protein binding is verified through point mutation of the key sites; determining a binding pocket, taking a drug in the ZINC22 small molecule drug database and a drug approved by FDA as ligand molecules, and taking the binding pocket as a docking region for virtual screening to obtain a compound; the obtained compound is screened through AMDET, and the screened medicine for inhibiting SOCS5-RBMX binding is capsaicin; capsaicin is used for carrying out in-vivo and in-vitro experiments for further screening verification; according to the method, the structure of the SOCS5-RBMX protein complex is analyzed, the binding structural domain and the key site are determined, virtual screening and experimental verification are carried out on the basis of the binding structural domain and the key site, the medicine for inhibiting SOCS5-RBMX binding can be accurately screened out, and the accuracy and efficiency of medicine screening are improved.

The application belongs to the technical field of molecular biology and drug screening, and provides a method for screening phenylhydrazine sulfate based on a key binding amino acid site of SOCS5-CP and application thereof, which comprises the following steps: key amino acid sites of SOCS5-CP binding are screened through alanine virtual point mutation, and a binding pocket is determined; a ligand molecule is used to perform virtual screening by taking the binding pocket as a docking area, and a compound with the best binding energy is obtained; the obtained drug is screened through AMDET; the selected compound is used for subsequent in-vitro cell experiments, and further screening is performed; the application uses the method of molecular docking and virtual screening in combination with in-vitro experiments for screening, and finds that phenylhydrazine sulfate can be stably combined at the key amino acid sites of SOCS5-CP, in-vitro experiments show that phenylhydrazine sulfate can effectively inhibit the binding of SOCS5-CP, and further down-regulate the protein expression level of HIF1a in hepatoma cells, and also has a significant inhibitory effect on the invasion and migration ability of primary hepatocellular carcinoma.

The invention discloses a biosensor responding to beta-alanine and application, and belongs to the technical field of bioengineering. A ligand binding pocket residue of BsGabR is subjected to mutation modification on the basis of a GABA biosensor, a BsGabR mutant capable of specifically recognizing and responding to beta-alanine and activating reporter gene expression is obtained through screening and iterative combinatorial mutation, the mutant is used for constructing a new biosensor, pregabalin can be efficiently and specifically responded, and the biosensor has a good application prospect. The method can be used for dynamic regulation and control of an amino acid metabolic pathway and a high-throughput screening platform of amino acid synthetase or strains, and has a relatively great application prospect.

The invention relates to the field of biological medicine and ophthalmic diseases, in particular to a target protein inhibitor for preventing and treating proliferative diabetic retinopathy and a screening method and application of the target protein inhibitor. The screening method comprises the following steps: 1) obtaining a three-dimensional crystal structure of CTSH; 2) constructing a binding pocket at an active site; 3) performing molecular docking and scoring on the small molecule library, and screening candidate compounds with binding energy lower than a preset threshold value; and 4) performing molecular dynamics simulation on the candidate compound and the CTSH compound, and selecting a compound with a stable structure and low binding free energy as an inhibitor. The inhibitor obtained by screening comprises eriodictyin, polygala tenuifolia sucrose ester B or an AP-III-a4 inhibitor. Genetic causal inference proves that CTSH has a causal driving effect on PDR, inflammation and pathological angiogenesis can be remarkably inhibited by regulating CTSH expression under a high glucose condition, and effective inhibitor components are finally screened.

The present application relates to a kind of target protein conformation targeting regulatory molecules and regulatory methods in living cells.The protein conformation targeting regulatory molecules include: 1) with the targeting group of selectively binding target protein as skeleton, 2) two active functional groups are modified on the skeleton, c) rigid connecting arm introduced between targeting group and active functional group.Based on the above characteristics, after the protein conformation targeting regulatory molecules of the cell are incubated with cell, they are rapidly combined with target protein in cell specifically through cell membrane, and covalent reaction occurs with amino acid near binding pocket, to target the conformation of target protein is regulated.According to the difference of protein conformation and reaction site, different active groups and rigid connecting arm are used, to realize the accurate regulation of target protein conformation in different functional states.The present application provides important technical support in the field of exploring protein conformation and function, expanding the library of druggable proteins, researching new use of old drugs, disease treatment or prevention.

The invention discloses a method for screening a small molecule compound capable of regulating and controlling brown adipose differentiation from ginsenoside and application of the small molecule compound. The present invention identifies a novel binding pocket in PPAR [gamma]-LBD. Through molecular docking, the Ginsenoside Rg3 is obtained by screening a plurality of ginsenosides, and experiments prove that the Ginsenoside Rg3 has relatively low toxicity to adipose-derived stem cells (ADSC) and can be used for remarkably activating an ADSC browning process at the same time.

The present application belongs to the field of bionic technology, and particularly relates to a kind of bionic material loaded with YD monomer and its preparation method and application.The present application utilizes YD monomer composed of tyrosine (Y) and aspartic acid (D) to synthesize a kind of bionic material through reversible addition-fragmentation chain transfer (RAFT) polymerization. The bionic material can produce spatially adjacent binding pockets through the covalent bond of tyrosine (Y) and aspartic acid (D), and can capture two kinds of PTM (phosphopeptide and O-glycopeptide) simultaneously through synergistic interaction. The results of the present application show that the bionic material of YD monomer optimizes charge balance, the neutral phenolic group of Y (pKa ~ 10) and the negatively charged carboxylate of D (pKa ~ 3.9) together reduce the electrostatic repulsion with phosphopeptide, while maintaining target affinity; self-assembled into nanostructured porous framework can expose multivalent binding sites, and significantly improve capacity and selectivity through synergistic effect.

The present disclosure relates to compounds of Formula (I): and pharmaceutically acceptable salts thereof, wherein Ring A, G1, RC, X, RD1, RD2, and RD3 are as described herein, methods of preparation and intermediates useful in said preparation, methods of treatment and prevention (e.g., of Caspase-4 mediated diseases and disorders), and pharmaceutical compositions comprising same. Compounds of Formula (I), and pharmaceutically acceptable salts thereof, are designed as selective Caspase-4 allosteric inhibitors, sparing Caspase-1, and have also been found to be selective against Caspase-5 and are thus, in embodiments, considered dual Caspase-4 / 5- inhibitors. The present disclosure further relates to the Applicant's discovery of a new and allosteric human Caspase-4 binding pocket, and methods of binding to (and compounds inhibiting the activity of) same, methods of treatment and prevention, and pharmaceutical compositions comprising such compounds.

The application relates to the field of biological medicines, and discloses a method for screening a TRPM8 antagonist, which comprises the following steps: step 1, contacting a candidate substance with a TRPM8 protein or a functional fragment thereof, wherein the TRPM8 protein or the functional fragment thereof at least contains 796D, 861Q and 862R amino acid residues; step 2, detecting whether the candidate substance is specifically combined with at least one residue in the TRPM8 protein or the functional fragment thereof; and step 3, if combined and at the same time can produce an allosteric effect on the protein, it can be preliminarily judged that the candidate substance is a TRPM8 antagonist. The application fills the gap of the existing technology about the TRPM8 binding mode and the screening method by disclosing the key residues and the allosteric binding pocket of the TRPM8 protein combined with the antagonist, and promotes the clinical application transformation of the TRPM8 antagonist in the fields of neuropathic pain, antitumor and bone repair.

Disclosed is a method of producing a non-naturally occurring peptide for reducing nitrogen, the method comprising: a) identifying a first group of peptides each having a binding pocket similar to a naturally occurring iron-sulfur cluster cofactor binding pocket of a naturally occurring nitrogenase, wherein each of the first group of peptides is not a nitrogenase or a subunit or domain of a nitrogenase; b) selecting, from the first group of peptides, a second group of peptides each having at least one target amino acid in the binding pocket; c) selecting, from the second group of peptides, a third group of peptides each having at least one target property; and d) modifying the sequence and / or structure of each of the third group of peptides to improve binding of the iron-sulfur cluster cofactor in the binding pocket. Also disclosed is a non-naturally occurring peptide for reducing nitrogen, comprising: at least one modification to a naturally occurring peptide; and a binding pocket for binding an iron-sulfur cluster cofactor; wherein the naturally occurring peptide is not a nitrogenase or a subunit or domain of a nitrogenase; and wherein the at least one modification improves binding of the iron-sulfur cluster cofactor in the binding pocket.

The present application belongs to the technical field of biotechnology and enzyme engineering, and relates to a molecular modification method for improving substrate specificity of aldehyde ketone reductase, which is achieved by constructing a substrate library of aldehyde ketone reductase AKR13B3 and analyzing kinetic parameters, determining a mutation site by performing loop structure analysis and amino acid sequence alignment on a complex structure of aldehyde ketone reductase AKR13B3, coenzyme NADPH and substrate 3-keto-DON, and screening a mutant with increased substrate specificity, the present application designs the geometric shape of the entrance loop region of the substrate binding pocket of AKR13B3 to change substrate preference and realize the increase of catalytic activity of the enzyme on specific substrates, in addition, the present application provides a feasible scheme for designing aldehyde ketone reductase with good substrate specificity, and provides great hope for developing high-efficiency enzyme preparations.

The invention relates to the field of costume design, in particular to an article loss prevention pocket which comprises a pocket and a binding pocket, and the binding pocket is formed by sewing two sides of a piece of cloth; the two ends of the binding bag are hollow; the periphery of the upper head of the binding pocket is fixedly connected with the periphery of the opening of the pocket; and a telescopic material is arranged on the periphery of the lower end of the binding bag.

The invention discloses a visual purple protein maximum absorption light wavelength prediction method based on a graph neural network. Comprising the following steps: generating a three-dimensional structure model according to an amino acid sequence of a to-be-predicted rhodopsin protein; generating a ligand pocket graph according to the three-dimensional structure model of the visual purple protein to be predicted; and inputting the ligand pocket graph into a pre-trained maximum absorption wavelength prediction model to obtain a maximum absorption wavelength prediction value. The method can make full use of protein three-dimensional structure information, accurately characterizes the ligand binding pocket microenvironment, has high prediction precision and strong generalization ability, and has important scientific significance and application value.

The invention belongs to the technical field of plant biology and agricultural biology, and relates to development and application of an FER kinase specific inhibitor FRV. Specifically, the invention provides an agricultural composition containing Forovicin, and provides an application of the agricultural composition in regulating and controlling an FER mediated signal channel and improving plants by combining the agricultural composition with an ATP binding pocket of FER to inhibit kinase activity. The invention provides an important tool for analyzing an FER signal mechanism and promoting agricultural application research.

The invention belongs to the technical field of molecular biology and drug screening, and provides a method for screening phenelzine sulfate based on SOCS5-CP key binding amino acid loci and application, and the method comprises the following steps: screening out SOCS5-CP binding key amino acid loci through alanine virtual point mutation, and determining a binding pocket; performing virtual screening by taking a binding pocket as a docking region through a ligand molecule to obtain a compound with optimal binding energy; the obtained medicine is screened through AMDET; carrying out subsequent in-vitro cell experiments by using the selected compounds, and carrying out further screening; screening is carried out by combining molecular docking and virtual screening methods with in-vitro experiments, it is found that phenelzine sulfate can be stably combined to key amino acid sites of SOCS5-CP, and in-vitro experiments show that phenelzine sulfate can effectively inhibit combination of SOCS5-CP, so that the protein expression level of HIF1a in hepatoma carcinoma cells is lowered, and the activity of the HIF1a in the hepatoma carcinoma cells is improved. And the compound also has a remarkable inhibition effect on invasion and migration ability of primary liver cancer.

The invention belongs to the field of biological medicine, and discloses a broad-spectrum anti-enterovirus peptidomimetic 2CA-1 targeting enterovirus 2C protein and application of the broad-spectrum anti-enterovirus peptidomimetic 2CA-1. The 2CA-1 can be accurately butted to 2C protein binding pockets of EV71 and CVB3, the helicase activity of the 2CA-1 is effectively inhibited, and the 2CA-1 shows a strong and broad-spectrum antiviral effect on various pathogens such as coxsackie virus, EV-D68 and rhinovirus on the cellular level. More importantly, the 2CA-1 realizes a druggability breakthrough of excellent oral bioavailability in an animal model, and the in-vivo virus load can be remarkably reduced after oral administration. The invention provides an antiviral candidate drug with high-efficiency broad-spectrum activity and ideal oral administration characteristics, and has a wide application prospect.

This invention discloses a high-yield canthaxanthin genetically engineered bacterium, its construction method, and its applications, relating to the fields of microbial metabolic engineering and synthetic biology. The construction method includes the following steps: introducing key genes into a yeast chassis strain for overexpression to obtain a basic canthaxanthin-producing bacterium; the key genes include... carB Gene, carRP Gene, crBKT Gene, HMG1 Genes and GGS1 Genes; through repeated gene introduction optimization, the quality of the cantharidin-producing strain was improved. crBKT The copy number of the gene was determined to obtain a copy number-optimized strain; the copy number-optimized strain was then... ERG7 The high-yield canthaxanthin genetically engineered bacterium was obtained by performing site-directed mutagenesis to shrink the substrate binding pocket of the gene. The high-yield canthaxanthin genetically engineered bacterium provided by this invention can significantly improve the synthesis efficiency and production yield of canthaxanthin, and has great application prospects in the field of canthaxanthin biosynthesis.

This invention discloses a drug-target interaction prediction method based on reparameterized convolution. This method is mainly aimed at virtual screening technology for drug lead compounds. It addresses the problem that many existing deep learning methods only learn high-dimensional representations of ligands and targets at a small scale, making it difficult for the model to obtain the potential patterns of binding pockets or multiple binding sites at a large scale. The invention introduces the reparameterized convolution method to improve the model's feature learning ability for protein targets and compound ligands. At the same time, a gated attention mechanism is designed to more effectively interact the characterization information of drugs and targets. The potential of this invention as a drug screening tool is verified through drug screening experiments on the target of Cystathionine-β-synthase (CBS).

The invention relates to the field of biological catalysis, and discloses a method for simulating and optimizing BHET degradation of acyltransferase through molecular dynamics, which comprises the following steps: taking a crystal structure or a homologous modeling structure of wild type MetA acyltransferase as an initial conformation, and utilizing a molecular dynamics simulation technology in the invention to simulate and optimize the BHET degradation of acyltransferase. The high flexibility of amino acid regions from the 188th site to the 290th site and the limiting effect of the amino acid regions on substrate binding are recognized, the space of a substrate binding pocket is physically expanded by selectively truncating a specific amino acid interval in a cap structure, and compared with wild-type MetA enzyme, the catalytic efficiency of the modified mutant in BHET hydrolysis reaction is improved by 3.13 times, and the yield of the mutant is increased by 30%. Under the optimal reaction condition, the mutant can efficiently convert 5mM BHET into MHET within 48 hours, so that the conversion process of PET degradation of an intermediate product is greatly accelerated, and an efficient way is provided for subsequent polymerization and reutilization.

The present application relates to the use of DDX39B protein inhibitor for preparing a therapeutic drug for acute leukemia, and belongs to the technical field of biological medicine. In order to solve the problem that the current treatment scheme for acute leukemia is single and new drugs are scarce, the present application provides the use of DDX39B protein inhibitor for preparing a therapeutic drug for acute leukemia. The present application discloses that targeted inhibition of DDX39B can significantly hinder the proliferation of leukemia cells, promote cell apoptosis and differentiation, block cell cycle progression, and delay disease progression and prolong the survival of model animals in vivo. Based on the RNA binding pocket structure of DDX39B, through high-throughput drug screening, the present application first identifies a small molecule compound HMU-4051C as a DDX39B targeted inhibitor that effectively kills leukemia cells, and develops a new use of DDX39B protein inhibitor in preparing a therapeutic drug for acute leukemia.

The invention generally relates to organic cages and in particular to alkali and alkline earth metal organic cages. The invention also relates to a method of making an organic cage, a method of lithium separation and use of an organic cage for lithium separation. The organic cage comprises at least one first ligand having at least one electron donating binding moiety, at least one second ligand having at least one electron donating binding moiety, and at least one metal ion selected from an alkali or alkaline earth metal ion, where the at least one first ligand and the at least one second ligand are covalently bonded such that they form a polyhedral cage having at least one binding pocket inside the polyhedral cage. Each of the at least one binding pockets has one electron donating binding moiety of at least one first ligand and one electron donating binding moiety of at least one second ligand, and each of the at least one metal ions is multiply coordinated to the binding moieties in one of the at least one binding pocket.