12 results about "Binding pocket" patented technology

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 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.

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.

Disclosed are a 1-deoxynojirimycin derivative and use thereof. According to the present invention, a variety of 1-deoxynojirimycin derivatives are prepared and obtained through screening. Compared with 1-deoxynojirimycin as a lead compound, the 1-deoxynojirimycin derivative can better bind to an amino acid site that is related to a target protein OPA1, stabilize a binding pocket at a dimer interface, promote the formation of an OPA1 dimer and repair a mitochondrial ultrastructure, thereby significantly saving mitochondrial functions and effectively improving a physiological state of cells. The 1-deoxynojirimycin derivative of the present invention can be used for preparing a drug for treating a disease that is related to unbalanced formation of the OPA1 dimer, and for example, can be used as a potential therapeutic drug for mitochondrial cardiomyopathy and other mitochondrial diseases.

Provided herein, in certain aspects, are methods for inhibiting a TNFR1 -mediated activity using a compound that binds to a binding pocket of TNFR1 between CRD3 and CRD4 of TNFR1.

This invention relates to mutant hydroxylase proteins and their applications. Specifically, it provides a mutant protein of the hydroxylase eryF, which has one, two, three, or more mutations in amino acids selected from the following regions: hydrogen bond network region, substrate binding pocket region, TTT region, and β11 region. These mutations can regulate the activity of the hydroxylase eryF, thereby controlling the production of its product EB.

This invention belongs to the field of molecular biology and drug screening technology, and provides a method for screening capsaicin targeting SOCS5-RBMX protein interactions and its application. The method involves analyzing the structure of the SOCS5-RBMX protein complex to determine the SOCS5-RBMX binding domain and key binding sites; verifying the inhibitory effect on protein binding through point mutations at these key sites; identifying the binding pocket; using drugs from the ZINC22 small molecule drug database and FDA-approved drugs as ligand molecules, and performing virtual screening with the binding pocket as the docking region to obtain compounds; screening the obtained compounds using AMDET to identify capsaicin as the drug inhibiting SOCS5-RBMX binding; and further screening and verification using capsaicin in in vivo and in vitro experiments. This invention, through the analysis of the SOCS5-RBMX protein complex structure to determine the binding domain and key sites, and then using this as a basis for virtual screening and experimental verification, can accurately screen for drugs inhibiting SOCS5-RBMX binding, improving the accuracy and efficiency of drug screening.

This specification provides a method for using compounds that bind to interleukin-1 beta (IL-1β) in the interleukin-1 beta (IL-1β) binding pocket identified herein, thereby capturing IL-1β and inhibiting its interaction with the interleukin-1 receptor type I (IL-1R1).

This invention discloses an engineered mutant CpAgo_PM based on a novel PAZ nucleic acid binding pocket and its applications, belonging to the fields of molecular biology and genetic engineering. The amino acid sequence of the mutant CpAgo_PM is shown in SEQ ID NO.1. This invention rationally designs the PAZ nucleic acid pocket, mutating some normally non-positively charged amino acid residues in the pocket to positively charged amino acids (CpAgo_PM). In in vitro cleavage experiments, four different target sites (TET2-1 / 2 / 3 / 4) on the human TET2 gene transcript were tested. Compared with CpAgo_WT, CpAgo_PM significantly improves the cleavage efficiency at three sites: TET2-1, TET2-2, and TET2-4, indicating that it partially overcomes the sequence cleavage bias of the wild type. Furthermore, its gene editing function in a eukaryotic cell environment has been clearly demonstrated.

This invention belongs to the field of intelligent cell biometrics, specifically involving a protein ligand pocket prediction method based on spatial gating and local feature enhancement. The method comprises four stages: data preprocessing and initial feature extraction, multi-scale feature encoding, spatially gating cross-layer feature fusion, and segmentation prediction based on depthwise separable convolution. This method integrates a Mamba module and a local feature enhancement module in the multi-scale feature encoding stage to achieve global modeling of protein features and adaptive enhancement of local features. Simultaneously, in the spatially gating cross-layer feature fusion skip connection stage, a spatially enhanced Mamba gating module is constructed to filter redundant information and enhance the fusion of multi-scale features. This invention effectively captures the long-range semantic information of proteins and intelligently filters and enhances cross-layer features, ultimately achieving protein ligand binding pocket prediction by generating a voxel-level probability map through depthwise separable convolution.

This invention discloses an enantioselective imine reductase mutant and its application in the production of S-arecoline, belonging to the field of enzyme engineering technology. The imine reductase mutant is obtained by single- or multi-point mutation of the substrate-binding pocket key amino acid site of wild-type imine reductase derived from *Pseudomonas* sp. RC4D1. This mutant can efficiently catalyze the asymmetric reduction of pseudo-arecoline, maintaining high enzyme activity while increasing the optical purity of the product S-arecoline to 99.9%. Combined with a glucose dehydrogenase coenzyme cycle system, it significantly reduces production costs. The reaction conditions are mild and environmentally friendly, enabling the industrial-scale production of S-arecoline and providing a high-purity raw material for fiber-free areca chewing gum.