1496 results about "Protein target" 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 discloses a protein palmitoyl transferase prediction method and system based on a multi-branch deep convolutional neural network, and belongs to the technical field of bioinformatics and artificial intelligence. The method comprises the following steps: S1, obtaining a to-be-detected protein sequence; s2, inputting the protein sequence into a pre-trained iPalmT model; and S3, judging whether the target protein is palmitoyl transferase or not according to a model output result. The iPalmT model comprises a coding module, two paths of parallel convolution branches, a feature fusion module and a classification module; and after the convolution layers of each convolution branch are stacked, an SE module is arranged and is used for channel weighting and feature re-calibration. The model extracts multi-level sequence features through convolution kernels of different scales, realizes high-precision prediction through feature fusion and a residual structure, can automatically learn multi-scale features from large-scale data, realizes end-to-end palmitoyl transferase recognition, and has high accuracy and good universality.

The invention discloses an mRNA non-coding region sequence optimization method and system and electronic equipment, and the mRNA non-coding region sequence optimization method comprises the steps: constructing an initial candidate library according to a target protein; inputting the initial candidate library into a pre-trained mRNA sequence optimization model to obtain a prediction data set; performing multi-dimensional scoring and sequence optimization on the prediction data set to obtain a sequence recommendation group; performing biological verification on the sequence recommendation group to obtain an optimized mRNA sequence; wherein the prediction data set comprises a sequence ID, a sequence content, a prediction TE score and a confidence interval. According to the method, the translation efficiency of the mRNA sequence can be efficiently and accurately predicted, the candidate sequence with high expression potential is screened out, meanwhile, the consumption of computing resources is reduced, and the overall design cost is reduced.

The invention relates to the field of artificial intelligence assisted drug discovery, in particular to a protein large language model-based molecule generation and optimization method, which comprises the following steps of: acquiring amino acid sequence information and three-dimensional structure information of a target protein pocket; encoding the amino acid sequence of the protein pocket by using a protein encoder constructed based on a protein large language model to obtain a protein pocket feature vector; using a context encoder module to encode the context information according to a preset molecule generation mode (de novo generation or optimization based on a seed compound) to obtain a latent vector; and fusing the protein pocket feature vector with the latent vector. According to the method, accurate representation of the protein pocket is realized by utilizing the protein large language model, and a generation-screening-optimization iterative drug design strategy is developed by supporting a unified framework of two generation modes, so that the targeting specificity of generated molecules and the overall efficiency of drug design are improved.

According to the GPX4 protein degradation agent and the application, the degradation agent serves as molecular glue to induce tumor cell ferroptosis and is different from an existing PROTAC technology, and the molecular glue can induce interaction between E3 ubiquitin ligase and target protein GPX4 and promote ubiquitination of the E3 ubiquitin ligase and the target protein GPX4. Compared with the existing GPX4 degradation agent, the molecular glue has the advantages of small molecular weight, high cell permeability and better druggability. The GPX4 molecular glue disclosed by the invention can be used for effectively degrading GPX4 and has a killing effect on various tumor cell lines. The preparation method is simple in synthesis route and mild in reaction condition, can be used for being developed into a new generation of GPX4 targeting drugs, and has great clinical application value and considerable market potential.

Provided are compounds that may bind a target protein, and result in modification of the target protein. The compounds may further bind a modifier protein. The modifier protein may carry out or enhance the modification of the target protein. The modification may activate or reactivate the target protein. Also provided are methods of using the compounds.

The invention provides a double-target degradation molecule based on a functionalized nucleic acid connexon and application thereof, and relates to the technical field of biological medicine, the double-target degradation molecule comprises an E3 ubiquitin ligase ligand at one end, a first target protein ligand at the other end, and the functionalized nucleic acid connexon located between the E3 ubiquitin ligase ligand and the first target protein ligand; the functionalized nucleic acid linker is a nucleotide sequence capable of specifically recognizing and combining a second target protein or a coding gene thereof, so that the protein level degradation of the first target protein and the nucleic acid level or expression level inhibition of the second target protein / gene are realized in the same molecule. Functionalized nucleic acid and a PROTAC strategy are organically combined, single-molecule double-target collaborative intervention is achieved, targeting efficiency and treatment potential are improved, higher flexibility and expandability are provided in synthesis and design, and a new molecular platform and technical route are provided for multi-target accurate treatment.

The invention discloses a shark source nano antibody targeting an FPV-VP2 protein and an application of the shark source nano antibody. The amino acid sequence of the complementarity determining region 3 of the shark source nano antibody is selected from any one of the sequences shown in SEQ ID NO.16 to SEQ ID NO.30, or a sequence having homology with the sequence shown in any one of the sequences shown in SEQ ID NO.16 to SEQ ID NO.30; the amino acid sequence of the shark source nano antibody is selected from any one of the sequences shown in SEQ ID NO.1-SEQ ID NO.15, or the amino acid sequence of the shark source nano antibody is selected from any one of the sequences shown in SEQ ID NO.1-SEQ ID NO.15, or a sequence having homology with the sequence shown in any one of the sequences shown in SEQ ID NO.1-SEQ ID NO.15. The shark source VNAR nano antibody has the advantages of small molecular weight, high affinity, high stability, easiness in genetic engineering modification, low production cost and the like.

Disclosed in the present invention is a novel substituted heterocyclic compound having VAV1 target degradation activity. Specifically disclosed is a compound serving as a VAV1 target degradation agent and having the structure of formula (I), or a pharmaceutically acceptable salt, solvate, hydrate, isotopic substituent or isomer of the compound. The compound can be used for preventing or treating diseases related to VAV1 targets or signaling pathways.

The invention discloses a novel benzofuran component in eupatorium chinense and application of the benzofuran component in anti-inflammatory activity. The obtained compound is separated from an eupatorium chinense extract. The eupatorium chinense root extract is separated by using an extraction method, macroporous adsorption resin impurity removal, Sephadex LH-20 gel column chromatography, high performance liquid chromatography and other methods. According to the present invention, all the separated compounds and the analogues thereof have good inhibition activity on target cyclooxygenase-2 of inflammation-related diseases, and have good inhibition activity on COX-2 enzyme, and the molecular docking experiment results show that the compounds and the target proteins have good binding energy. Therefore, the compound can be used for preparing drugs for treating inflammatory related diseases, or anti-inflammatory and analgesic drugs, or tumor drugs by inhibiting COX-2 enzyme, such as drugs for rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, Alzheimer's disease and the like, and related natural lead compounds are provided.

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 discloses a chimera for degrading a CARD structural domain protein aggregate and application of the chimera. The chimera is prepared from light-operated targeting protein and light-operated degradation protein, the light-operated targeting protein is sequentially connected by an MAVS CARD structural domain, a flexible connecting peptide and a photosensitive protein pMag; the light-controlled degradation protein is sequentially connected by a photosensitive protein nMag, a flexible connecting peptide and an RING structural domain of TRIM21. According to the application, a light-operated activated CARD-RING chimera is constructed, and when the CARTAC generates toxic and side effects or in cells with RIG-I / MDA5 signal channels abnormally activated, the activity of the CARTAC can be effectively controlled or autoimmune diseases caused by RIG-I / MDA5 abnormity can be inhibited.

The invention provides a cell protein degradation platform based on an artificial biological macromolecular aggregate. Specifically, the invention provides a PROTAC functional module based on an interworking nucleic acid skeleton, a PROTAC-aggregate complex (MLO-PROTAC), a kit, application and a preparation method of the PROTAC functional module, the PROTAC-aggregate complex (MLO-PROTAC) and the kit, and also provides a targeted protein degradation method. In a PROTAC platform built by the PROTAC functional module and the PROTAC-aggregate complex, a programmable nucleic acid component is used as a core assembly unit, and the functional module is enriched and spatiotemporal-spatial regulation is performed by using the polypeptide aggregate, so that the delivery efficiency and the cytoplasm exposure degree are remarkably improved while the universality is maintained, and the delivery efficiency and the cytoplasm exposure degree are remarkably improved. Therefore, a more effective target protein degradation way is provided for the field.

Disclosed herein are predictive models for T-cell epitope prediction, B-cell epitope prediction, and protein design wherein a method is implemented for generating a protein variant amino acid sequence of a target protein having one or more modified properties, the method comprising: (a) iteratively sampling an input amino acid sequence of the target protein, and (b) sampling the individual protein score of at least one weighted relative contribution of the single residue mutant input amino acid sequence to the at least one target property across a plurality of other single residue mutant input amino acid sequences to generate a combined protein score, wherein the combined protein score corresponds to the protein variant comprising one or more amino acid mutations of the single residue mutant input amino acid sequences.

The invention discloses an oligonucleotide intracellular nano delivery system based on polypeptide modification and application thereof. The system is composed of a periostin targeting sequence (SDSSD), a matrix metalloproteinase 2 (MMP2) response sequence (GPAGLLG), a cell penetrating sequence (RRRRRRRR, R9), a reactive oxygen species (ROS) scavenging and adhesion enhancing group (Gly-DOPA)) and a terminal dibenzocyclooctyne (DBCO) modified engineered polypeptide SDSSD-PEG5-YGFGG-GPAGLLG-R9-(G-DOPA) 3-K4-C-DBCO, and a target oligonucleotide miRNA-26a-A5-Azido modified by 5-polyadenylic acid (AAAAA) and an azide group (Azido), and the target oligonucleotide miRNA-26a-A5-Azido, the target oligonucleotide and assembling through a click chemical reaction and a non-covalent interaction. The nano system has good bone targeting, enzyme responsiveness, intracellular delivery effect and biological safety, can realize stable and efficient delivery of therapeutic oligonucleotides in vivo, and significantly improves the utilization efficiency and therapeutic potential of oligonucleotides. The oligonucleotide intracellular nano delivery system has a wide application prospect in the fields of clinical transformation and precise treatment of oligonucleotide drugs.

The invention provides a disease marker epitope prediction and antibody screening method, which belongs to the technical field of disease markers, and comprises the following steps: firstly, establishing a training data set containing a known antigen-antibody compound structure and disease tissue expression data; and obtaining target protein sequence information through liquid chromatography-mass spectrometry analysis and carrying out sequence comparison. And then a deep convolutional neural network is utilized to extract sequence features, and surface exposure sites are identified by combining secondary structure prediction and solvent accessibility analysis. After the features are integrated with sequence evolution conservative properties, a prediction model is constructed by using a random forest classifier. The method comprises the following steps: carrying out molecular dynamics simulation on a prediction result, screening first 10% of candidate sequences through a comprehensive scoring function and K-means clustering, and finally determining an antigen epitope sequence with the strongest binding activity through verification of an antigen chip and a fluorescence labeled antibody system, so that the technical problem that specific antigen epitopes are difficult to accurately predict and recognize in the prior art is solved.

The invention belongs to the technical field of biological medicine, and particularly relates to an engineered cell microvesicle and a delivery system based on the engineered cell microvesicle, the system realizes efficient preparation of 1-5 [mu] m cell microvesicles, and the cell microvesicles have a large space volume and can be used for preparing the cell microvesicles. The carrier can be used for loading and delivery of target protein, polypeptide and recombinase which are specifically expressed in mother cells. The system transfects mother cells through lentivirus transfection or plasmid transfection to further produce cell microvesicles, and the microvesicles can load more goods and inherit membrane proteins of the mother cells, and can also effectively load intracellular proteins to realize effective delivery. By virtue of good structural stability, high immunogenicity and excellent biocompatibility, the cell microvesicle reduces systematic toxic and side effects of a traditional carrier, is expected to become an effective drug delivery system, and has great application potential in the field of gene therapy.

The invention discloses application of a target protein circPIAS1-108aa inhibitor combined with oxaliplatin in preparation of a medicine synergistic composition for treating cancers, the specific action mechanism of circPIAS1-108aa in colon cancer treatment is found for the first time, and further research shows that by using siRNA to knock down circPIAS1-108aa, colon cancer cell proliferation can be remarkably inhibited, and the effect of treating the colon cancer can be achieved. Furthermore, the target spot protein circPIAS1-108aa inhibitor can be used for enhancing the treatment effect of the oxaliplatin. Therefore, when the circPIAS1-108aa expression is inhibited in a targeted manner and the oxaliplatin is combined for use, the circPIAS1-108aa can be obviously used for preventing and treating cancers, the dosage and toxic and side effects of the oxaliplatin are reduced, and a new synergistic strategy is provided for tumor treatment.

The present disclosure relates to methods of identifying RNA targets of RNA binding proteins. In aspects, the disclosure relates to a method of identifying RNA molecules bound by RNA binding proteins. Some embodiments of the present disclosure relate to a method that can definitively identify direct RNA-target interactions with targeted proteins without the requirement for immunoprecipitation or gel extraction. In some embodiments, the method may include combining multiple antibodies in the same sample.

The invention provides antibody conjugate compositions of Formula I comprising an antibody linked by conjugation to one or more target protein binder and VHL ligand (TPI-VHL) moieties. The invention also provides TPI-VHL derivative intermediate compositions comprising a reactive functional group. Such intermediate compositions are suitable substrates for formation of the antibody conjugates through a linker or linking moiety. The invention further provides methods of treating diseases and disorders such as cancer with the antibody conjugates.

The invention discloses a method for improving the solubility and thermal stability of sweet protein, and belongs to the technical field of biosynthesis, the method comprises the following steps: constructing a gene tandem recombinant plasmid containing a monellin x-3C-sfGFP-3C-monellin y expression cassette, x is greater than or equal to 1, y is greater than or equal to 1, 5 is greater than or equal to x + y is greater than or equal to 3, a 3C protease recognition sequence is also inserted between adjacent copies of monellin, and each monellin is connected with a purification tag; the gene tandem recombinant plasmid is transformed into escherichia coli and inducible expression is carried out, thalli are split and purified to obtain fusion protein, 3C protease is used for enzyme digestion, and the target protein is obtained after re-purification. The total protein yield and the solubility proportion are remarkably improved by adopting a series construction mode of plasmids, meanwhile, the stability of monellin is effectively improved, the purification step is simpler and more convenient, and the method is suitable for industrial production.

The invention discloses a nanoparticle for targeted protein degradation and a degradation method. The nanoparticles can enhance uptake of cells and effectively encapsulate specific antibodies for recognizing target proteins, and meanwhile, the interferon component can induce expression of TRIM family proteins in the cells. After ingestion into the cell, the antibody released by the nanoparticle can bind to the target protein and bind to the TRIM family protein to mediate degradation of the target protein. In this process, although the TRIM family protein is continuously consumed, the TRIM family protein can be compensated by the TRIM family protein expression induced by the particle of the invention, thereby maintaining efficient degradation.

The invention discloses a drug delivery system based on branched chain nucleic acid as well as a preparation method and application of the drug delivery system. The drug delivery system comprises a multivalent nucleic acid framework, a nucleic acid-small molecule coupling drug and a nucleic acid-polypeptide coupling drug, a nucleic acid nanostructure is formed through base complementary pairing assembly, and the nucleic acid-small molecule coupling drug comprises first nucleic acid and an E3 ubiquitin ligase ligand coupled with the first nucleic acid; the nucleic acid-polypeptide coupling drug comprises a second nucleic acid and a cell penetrating peptide coupled with the second nucleic acid. The drug delivery system disclosed by the invention can respond to a tumor microenvironment, so that cell penetrating peptides are activated, tumor penetrating and cytoplasm delivery capacities are enhanced, the aim of efficiently degrading tumor-related target proteins is fulfilled by combining a multivalent effect, and a remarkable tumor treatment effect is achieved; in addition, the preparation method is simple and easy to implement, has universality and high production efficiency, and is expected to be applied to treatment of various tumors.

The present invention relates to a novel regulatory element. The regulatory element according to one embodiment is capable of increasing RNA stability or mRNA translation of a transcription product of a target gene, thereby being capable of increasing the expression level of the target protein, and can be effectively used in systems requiring precise control of gene expression, such as gene therapy, vaccine development, and production of protein therapeutics. Furthermore, the regulatory element of the present application exhibits excellent stability-increasing ability and translation-regulating ability not only in unmodified RNA but also in RNA containing a modified base, and thus can be effectively used in therapeutic mRNA or vaccine platforms requiring base modification.

The present disclosure relates to a novel class of bifunctional molecules that are useful in a targeted or selective degradation of a protein.

The invention relates to the technical field of drug target prediction, and discloses a drug target intelligent prediction method and system, and the method comprises the following steps: 1, obtaining the structure data and sequence data of a target protein, and the homologous sequence data of the target protein; 2, performing molecular dynamics simulation according to the structural data, and calculating to obtain a dynamic conformation feature vector; according to the sequence data, an evolutionary information feature vector is obtained through calculation; analyzing the structural data to obtain an interaction feature vector; 3, obtaining an enhanced dynamic conformation feature vector, an enhanced evolutionary information feature vector and an enhanced interaction feature vector through an attention fusion mechanism, respectively obtaining importance weights through a gating fusion mechanism, and obtaining a fusion feature vector by adopting element-by-element multiplication and combining the importance weights; and 4, inputting the fusion feature vector into a graph neural network prediction model to obtain a target druggability probability.

The invention discloses a functional protein screening method based on a large language model, and belongs to the technical field of protein screening, and the method specifically comprises the following steps: obtaining a protein three-dimensional structure and functional literature, converting the protein three-dimensional structure and functional literature into a multi-modal feature vector by using an encoder, and constructing a domain-specific vector database; after a screening instruction is received, related feature data of semantic matching is called through a vector retrieval algorithm; then, inputting the data into a large language model to execute biological mechanism reasoning, and outputting an initial candidate protein sequence containing predicted activity; further, physical binding energy is calculated by using a molecular docking program, a deviation coefficient between the physical binding energy and the predicted activity is generated, and the coefficient is used as a penalty term to construct a dynamic correction function to update the scoring weight; and finally, performing secondary sorting on the candidate set based on the updated weight, and outputting the sequence sorted for the first time as a target protein. According to the method, AI reasoning and physical verification are effectively combined, and the screening accuracy is improved.

The invention relates to a recombinant vector for expressing natural long-sequence recombinant XVII type collagen as well as a preparation method and application of the recombinant vector, and relates to the field of protein. The nucleotide sequence for optionally coding the recombinant XVII type collagen has at least one section of nucleotide sequence for coding the amino acid sequence as shown in SEQ ID NO: 1 (optionally has at least one section of nucleotide sequence as shown in any one of SEQ ID NO: 2 to SEQ ID NO: 4). The produced target protein is excellent in safety performance, shows huge potential in a plurality of application scenes such as plastic surgery, hair regeneration and the like, is expected to break through previous dilemma, truly opens a new chapter of commercialized application of the recombinant COL17 protein, and injects brand new vitality to related industries.

The invention discloses an LbCas12a protein mutant as well as a preparation method and application thereof, the LbCas12a protein mutant is obtained by performing K390A or K945A mutation on a wild type LbCas12a protein, and the amino acid sequence of the wild type LbCas12a protein is as shown in SEQ ID NO. 1. According to the present invention, the LbCas12a protein is subjected to directional modification, the alanine mutation occurs at the K390 / K945 site, the LbCas12a-K390A protein mutant and the LbCas12a-K945A protein mutant are prepared, the protein mutants obtained based on the method provide a series of significant advantages in function, and the solid foundation is laid for the application of the protein mutants in multiple fields. Through Michaelis-Menten kinetic analysis, it is observed that when the LbCas12a-K390A / K945A protein mutant prepared through the method and the wild type LbCas12a protein target the same dsDNA target, the catalytic efficiency of the LbCas12a-K390A / K945A protein mutant is 42.1 times that of the wild type LbCas12a, and the catalytic efficiency of the LbCas12a-K390A / K945A protein mutant is 707.9 times that of the wild type LbCas12a, and the catalytic efficiency of the LbCas12a-K390A / K945A protein mutant is 707.9 times that of the wild type LbCas12a. The results show that K390 and K945 are mutated into alanine, so that the affinity of the LbCas12a protein to a substrate can be increased to a certain extent, and the LbCas12a protein has higher trans-cleavage activity.

The invention belongs to the technical field of medicines, and particularly relates to a PARP-1 protein targeted degradation chimera compound as well as a preparation method and application thereof. The PARP-1 protein targeted degradation chimera compound is as shown in a formula (I), wherein P represents a ligand of PARP protein, Z represents a ligand of E3 ligase, and L represents a middle connecting chain part; the compound can be used for treating or preventing tumors. The PARP-1 protein targeted degradation chimera disclosed by the invention has a relatively good inhibition effect on proliferation of tumor cells, has a very high degradation effect on PARP-1 protein, and has concentration gradient dependence. (I).