33 results about "Small molecule binding" patented technology

Disclosed is a computer-implemented method for identifying small molecule binders within a DNA-encoded library (DEL) dataset. Said method comprises: obtaining a DEL dataset comprising enriched compounds; grouping enriched compounds into one or more compound groups based on a grouping criterion selected from at least one of: chemotype, library, enrichment level, or linear feature; generating a plurality of three-dimensional (3D) conformers, for each enriched compound in each compound group; comparing generated 3D conformers within one or across two or more compound groups to identify consensus overlays based on similarity metrics exceeding a predefined threshold; and selecting small molecule compounds forming said cross-group consensus overlays as small molecule binders having affinity for a target of interest. Disclosed also is a system for identifying small molecule binders within a DEL dataset. Said system comprising: a processor configured to perform aforementioned steps of method and an interface for displaying selected small molecule binders.

Disclosed herein is an adenoviral vector system utilizing DARPin adapters. The system is highly effective, safe and able to deliver DNA in a cell-specific manner. It is demonstrated that the system is unexpectedly versatile, and can be used in conjunction with protein scaffolds, bioactive peptides and small molecules. This makes the system useful for numerous purposes, including the use of the system for therapeutic and diagnostic purposes.

The invention discloses a protein and small molecule binding structure prediction method, device, equipment and medium, and relates to the technical field of protein and small molecule binding prediction.The method comprises the steps that a first modeling graph structure and a second modeling graph structure after a protein block and a to-be-tested small molecule compound are modeled respectively are obtained; the first modeling graph structure and the second modeling graph structure are input into a TANKBind model, and a predicted protein small molecule compound is output through the TANKBind model; generating a first topological file and a second topological file corresponding to the protein structure file and the small molecule structure file of the protein small molecule compound; performing molecular dynamics simulation by using a preset molecular dynamics simulation tool according to a simulation file generated by the first topological file and the second topological file to obtain a molecular dynamics simulation track file; and analyzing the molecular dynamics simulation track file, the first topology file and the second topology file to obtain a simulation analysis result.

This application provides a method for screening inhibitors targeting CYP7A1 and their use in the preparation of anti-liver cancer drugs, relating to the field of tumor targeted drug design technology. The method for screening inhibitors targeting CYP7A1 protein includes: using the crystal structure of human cholesterol 7α-hydroxylase as a receptor model, precise docking screening is performed using software to screen drug-like molecules with molecular weights of 250-500 Da and lipid-water partition coefficients of -1 to 5 from a compound database; a graph neural network active learning model is used to predict and rank the protein-small molecule binding affinity of compounds in the database; the ΔG between candidate molecules and CYP7A1 is calculated using molecular mechanics / generalized Born surface area methods, with molecules having ΔG ≤ -40 kcal / mol considered potential inhibitors. The inhibitors of this application do not rely on the enzymatic activity of CYP7A1 to achieve anti-tumor effects and do not significantly affect cholesterol and bile acid metabolism levels.

The application provides a mass spectrometry detection device and method for active protein-small molecule interaction, which uses a mass spectrometry sensor to obtain tandem mass spectrometry data of non-covalent complexes of active protein incubated with small molecule compounds at different concentration points; performs non-linear curve fitting on the concentration sequence of the small molecule compounds based on the ion combination rate of the protein binding small molecules at each concentration point, to obtain an apparent dissociation constant of the active protein-small molecule interaction; determines a local conformation change parameter of the active protein induced by small molecule binding and a potential binding domain of the small molecule; and performs fusion evaluation on the binding strength and conformation influence degree of the protein-small molecule interaction based on the apparent dissociation constant, the local conformation change parameter and the potential binding domain, to output a stability grade of the protein-small molecule interaction. Based on the above scheme, non-denatured state mass spectrometry detection of protein-small molecule complexes in a liquid phase environment can be realized.

A high-throughput screening system and method for small molecule-protein interactions includes first immobilizing selected small molecules on a solid matrix. Immobilization is preferably performed via photoaffinity labeling, where a linker is used to bind the small molecule to the matrix. cDNA libraries are constructed based on various human tissues. Tissue mRNA is transcribed into cDNA and transferred to a phage genome to construct a phage display library, which is then mixed with small molecules conjugated to microspheres and incubated. The incubated mixture is washed to remove unbound phages, including non-specific and weakly bound phages. Bound phages are amplified and used for the next round of biopanning. The biopanning cycle is repeated, and then PCR is performed on each plaque obtained from the final round of biopanning. The PCR products from each small molecule experiment are barcoded, merged, and then subjected to next-generation sequencing.

The present disclosure relates to oligonucleotide aptamers that bind to certain small molecules including thiamine analogs and derivatives and methods of generating aptamers that bind to the small molecules. Also contemplated are riboswitches and polynucleotide cassettes comprising the aptamers disclosed herein. Further provided are methods of using said aptamers, riboswitches, and / or polynucleotide for the regulation of target genes, including therapeutic genes. Also provided herein are small molecules that are modulators of target gene expression where the target gene contains a riboswitch comprising an aptamer described herein.

The invention discloses a small molecule binding protein design method. The method comprises the following steps: S1, a structure acquisition step: acquiring a compound structure of a target small molecule ligand and protein; s2, a candidate sequence generation step: generating a candidate protein sequence set by adopting a protein generation model and adjusting parameters corresponding to the protein generation model according to the compound structure in the step S1; s3, a primary screening step; compounding the candidate protein sequence set in the step S2 with the small molecule ligand in the step S1, predicting a compound structure I, and screening a potential sequence from the compound structure I; s4, a fine screening stage: compounding the potential sequence screened in the step S3 with the small molecule ligand in the step S1, predicting a compound structure II, and screening a preferred protein sequence I from the compound structure II. Through deep fusion of AI generation and physical screening, a layer-by-layer progressive accurate screening funnel is constructed, and the false positive rate is greatly reduced.

This invention relates to the field of anti-aging drug technology, specifically to the application of small molecule compounds in the preparation of anti-aging drugs. These small molecule compounds competitively block the interaction between KDM6A and the vacuolar ATPase V0 domain subunit ATP6V0C by targeting a specific small molecule binding pocket of the histone demethylase KDM6A, thereby inhibiting the demethylation activity of KDM6A on lysine residue 36 of ATP6V0C. These small molecule compounds can effectively downregulate aging-related β-galactosidase activity, improve cell cycle arrest, and reverse the senescent phenotype of nerve cells induced by the environmental pollutant GenX, making them particularly suitable for combating premature aging of nerve cells induced by perfluorinated and polyfluoroalkyl compounds such as GenX. This technical solution can solve the technical problem of the lack of drugs with clearly defined components, a clear mechanism of action, stable efficacy, and the ability to specifically alleviate aging in existing technologies, and has ideal prospects for widespread application.

The present disclosure relates to method and system (104) for sampling datasets for identification of druggable sites in Ribonucleic Acids (RNAs). The method comprises receiving, by a system, a dataset of RNA structures bound to small molecules, from one or more sources. Further, the method comprises determining a plurality of binding sites from the dataset, based on a spatial proximity threshold between the RNA structures and ligand atoms. A set of structural features are determined from the plurality of binding sites to obtain a positive dataset of druggable sites. A plurality of negative binding sites are predicted based on the positive dataset of druggable sites. A non-redundant negative dataset is generated by resolving inter-source and intra source redundancy among the plurality of negative binding sites, wherein the non-redundant negative dataset is used with the positive dataset to train an ML model for identification of the druggable sites in the RNA structures.

The invention relates to the technical field of anti-aging drugs, in particular to application of a small molecule compound in preparation of anti-aging drugs. The small molecule compound competitively blocks the interaction between the KDM6A and a vacuolar ATP enzyme V0 structural domain subunit ATP6V0C through a specific small molecule binding pocket of targeted histone demethylase KDM6A, and further inhibits the demethylation activity of the KDM6A on 36th lysine of the ATP6V0C. The small molecule compound can effectively down-regulate the activity of senescence-related beta-galactosidase, improve cell cycle arrest and reverse nerve cell senescence phenotypes induced by environmental pollutant GenX, and is especially suitable for resisting nerve cell premature senescence caused by perfluorinated and polyfluoroalkyl compounds such as GenX. According to the technical scheme, the technical problem that drugs which are definite in component, clear in action mechanism, stable in curative effect and capable of pointedly relieving senescence are lacked in the prior art can be solved, and ideal application and popularization prospects are achieved.

In alternative embodiments, provided are synthetic, or non-natural, protein heterodimers or homodimers whose protein / protein binding interactions are controlled through metal or small molecule binding, and methods of making and using them. In alternative embodiments, provided are metal-controlled or small molecule-controlled heterodimers or homodimers, wherein each dimer is fused or joined to half or a portion of a detectable entity, and the when the two dimers are joined or come in contact with each other because of each dimer's binding to a metal, the detectable entity's halves, now also joined or having come in contact with each other, only now can directly or indirectly generate or initiate a detectable signal. In alternative embodiments, provided are biosensors or microfluidic devices comprising synthetic, or non-natural, protein heterodimers or homodimers as provided herein.

The application discloses an application of a small molecule compound in preparation of an IL-6R inhibitor and belongs to the technical field of medicines. Through various calculation methods and in-vitro experiments, two novel small molecule compounds targeting IL-6R are successfully identified, and are named as Z1268663363 and Z1268663684 respectively. The small molecule compound can inhibit IAV and SARS-CoV-2 induced IL-6 signaling pathway, and phosphorylation of STAT3, JAK2 and gp130 induced by IL-6. In addition, the small molecule compound can inhibit IL-6 stimulated TF-1 cell proliferation and block the binding of IL-6 and IL-6R. In addition, MD simulation confirms the spontaneous and sustained binding between the compound and IL-6R. The research reveals the flexible binding site of IL-6R, and determines a promising small molecule binder, and promotes the development of new drugs for IL-6 related diseases.

Dysregulated IL-4 signaling contributes to a number of immune-mediated diseases such as allergic inflammation, cancer, and autoimmunity. The present disclosure provides small molecule binders and inhibitors of IL-4, and pharmaceutical compositions, kits, and uses thereof.

Small molecules for targeting the 5'UTR to modulate oncogenic protein expression levels and methods thereof are described. These small molecules are inhibitors of BMI 1 expression and may be useful in the treatment of cancer. Also disclosed are small molecule probes to map binding sites and small molecule binding.

The invention belongs to the technical field of computers and bioinformatics, and relates to a protein-small molecule binding site prediction method, in particular to a protein-small molecule binding site prediction method based on real-time feature decoupling and evidence deep learning. Obtaining an amino acid sequence of a target protein, and generating a dense embedding vector for each residue; carrying out decoupling processing to generate sparse features, and extracting task specific features; and inputting the data into a parallel double-output-head framework, and optimizing the whole model by adopting a collaborative loss function based on the uncertainty of non-negative evidence value quantitative prediction. According to the method, the accuracy of binding site prediction is remarkably improved, the decoupled features have clear biological significance, reliable theoretical support is provided for subsequent drug molecule design and binding mechanism analysis, the situation that subsequent experiment design is misled by unreliable prediction is effectively avoided, waste of research and development resources is reduced, the scientificity and safety of decision making are improved, and the method is suitable for large-scale popularization and application. The method has important theoretical significance and practical value.

The invention provides screening of a targeted CYP7A1 inhibitor and application of the targeted CYP7A1 inhibitor in preparation of anti-hepatoma drugs, and relates to the technical field of tumor targeted drug design. The screening method of the CYP7A1 protein targeting inhibitor comprises the following steps: taking a human cholesterol 7alpha-hydroxylase crystal structure as a receptor model, carrying out accurate docking screening through software, and screening drug-like molecules with the molecular weight of 250-500Da and the fat-water partition coefficient of-1-5 from a compound database; a graph neural network active learning model is adopted, and protein-small molecule binding affinity prediction and sorting are carried out on the compounds in the database; the delta G of the candidate molecules and CYP7A1 is calculated through a molecular mechanics / generalized Born surface area method, and the molecules with the delta G smaller than or equal to-40 kcal / mol are potential inhibitors. The inhibitor provided by the invention realizes the anti-tumor effect without depending on the enzyme activity function of CYP7A1, and does not obviously influence the cholesterol and bile acid metabolism level.

In certain examples, methods and apparatuses are directed to small molecules (e.g., drug-like molecules) binding to a target protein in live cells. In a specific example, a method includes: processing a laser beam, from a quantum cascade laser (QCL), carrying light in a wavelength range that overlaps a mid-IR range; using optics, in response to the laser beam, to process the light in a set of related beams along respective paths, including a reference path and a sample path, respectively towards a reference target and a sample target that includes living cells: and detecting, via a vibrational spectroscopy detector, small molecules binding to a target protein in live cells. The detection is carried out by collecting incident light, relative to the reference target and from the sample target, carried along respective incident paths and by discerning (e.g., measuring) vibrational probe frequency shifts in the sample target.

RNA drug targets are pervasive in cells but methods to design small molecules that target them are sparse. Herein, we report a general approach to score the affinity and selectivity of RNA motif-small molecule interactions identified via selection. Named High Throughput Structure-Activity Relationships Through Sequencing (HiT-StARTS), HiT-StARTS is statistical in nature and compares input nucleic acid sequences to selected library members that bind a ligand via high throughput sequencing. The approach allowed facile definition of the fitness landscape of hundreds of thousands of RNA motif-small molecule binding partners. These results were mined against folded RNAs in the human transcriptome and identified an avid interaction between a small molecule and the Dicer nuclease-processing site in the oncogenic microRNA (miR)-18a hairpin precursor, which is a member of the miR-17-92 cluster. Application of the small molecule, Targapremir-18a, to prostate cancer cells inhibited production of miR-18a from the cluster, de-repressed serine / threonine protein kinase 4 protein (STK4), and triggered apoptosis. Profiling the cellular targets of Targapremir-18a via Chemical Cross Linking and isolation by Pull Down (Chem-CLIP), a covalent small molecule-RNA cellular profiling approach, and other studies showed specific binding of the compound to the miR-18a precursor, revealing broadly applicable factors that govern small molecule drugging of non-coding RNAs.

The invention relates to a small molecule detection method and system and application, belongs to the technical field of biological detection, and solves the problems of high cost, complex design and operation and poor sensitivity of the existing method. The small molecule detection method comprises the following steps: constructing activated double-stranded DNA of Cas12a; the method comprises the following steps: modifying a to-be-detected small molecule at the 3'tail end of a Scaffold chain to synthesize a Scaffold-to-be-detected small molecule chain; providing a macromolecule, a spacer chain and a signal report probe which can be combined with a small molecule to be detected to form steric hindrance; the method comprises the following steps: respectively diluting a Cas12a enzyme, dsDNA-TS, dsDNA-NTS, a scaffold-to-be-detected small molecular chain, a macromolecule, a spacer chain, a to-be-detected small molecule and a signal report probe to specified concentrations; mixing the scaffold-to-be-detected small molecular chain, to-be-detected small molecules and macromolecules, and reacting in a competitive binding reaction system; and performing fluorescence detection.

Dysregulated IL-4 signaling contributes to a number of immune-mediated diseases such as allergic inflammation, cancer, and autoimmunity. The present disclosure provides small molecule binders and inhibitors of IL-4, and pharmaceutical compositions, kits, and uses thereof.

The application discloses a DNA binding small molecule high-throughput screening and characterization method, adopts a small molecule binding agent to program a toehold-mediated strand displacement (TMSD); performs one-stop comprehensive characterization of the interaction between the small molecule binding agent and double-stranded DNA, including dissociation constant, binding site size, thermodynamic parameters and sequence selectivity; performs high-throughput screening (HTS) identification of the small molecule binding agent by using a series of induced nucleic acid displacement BIND reaction system; and combines experimental measurement and computer simulation, and it is shown that the small molecule double-stranded DNA binding agent can be used in the reaction path of programming toehold-mediated strand displacement (TMSD), so that the molecular tool of comprehensive thermodynamic characterization can be performed by using the binding agent induced nucleic acid displacement (BIND) technology, and the high-throughput screening (HTS) of the small molecule double-stranded DNA binding agent can be performed without any special equipment, the application is widely used as a one-stop HTS and comprehensive characterization platform, so as to accelerate the pace of discovering novel small molecule double-stranded DNA binding drugs / tracers.

This application relates to the field of biomedical technology, proposing a compound that targets and degrades RALBP1 protein, its preparation, and its application. The compound is the compound shown in formula (I), or its tautomers, stereoisomers, hydrates, solvates, pharmaceutically acceptable salts, or prodrugs. The compound of this application belongs to the PROTAC drug category, which can target small molecule conjugates of RALBP1, thereby inducing RALBP1 degradation and achieving effective prevention or treatment of acute myeloid leukemia. Simultaneously, the compound of this application can be used in oral formulations; through structural optimization, it balances drug activity and oral convenience. Single or multiple administrations can produce significant tumor-suppressive effects, demonstrating broad application prospects. (I)

The present invention relates to a method for identifying which members of a barcode-free library of small molecules bind to a target and elucidating their molecular structure, the method comprising: a) mixing the members of at least one subset of the library with the target; b) separating the members that do not bind to the target (nonbinders) from the members that bind to the target (binders); c) analysing the binders using tandem mass spectrometry (MS / MS) to generate MS / MS spectra of the binders; and d) analysing the MS / MS spectra by computational analysis to elucidate the molecular structure of the binders.

This application belongs to the field of biotechnology, specifically relating to a method for identifying the binding sites of proteins and small molecules. This application utilizes ultrafiltration to effectively separate double-enzyme digestion products, simplifying sample processing, reducing sample complexity, and lowering the difficulty of data analysis, resulting in more efficient and accurate mass spectrometry data interpretation. Compared to existing restriction enzyme-based methods, this application, through double-enzyme digestion technology, can capture more subtle differences in the binding of proteins and small molecules, improving the accuracy of target protein identification.

The present invention discloses a method and system for predicting RNA-small molecule binding sites. The method comprises obtaining global information and local information based on a motif of a full-length RNA and a motif of its local neighboring RNAs; inputting the global information into a two-dimensional feature fusion network to obtain global features, wherein the two-dimensional feature fusion network includes a convolutional neural network channel and an attention network channel; inputting the local information into a fully connected neural network to obtain local features; inputting the fused feature information after integrating the global features and the local features into an Inception module of a one-dimensional feature fusion for deep fusion to obtain deep fusion features; and inputting the deep fusion features into an output layer to predict the probability value of the binding site. The present invention greatly improves the effective utilization of RNA feature information and reduces the number of parameters, so that the network can maintain the prediction performance of RNA-small molecule binding sites while also being lightweight.

The invention belongs to the field of intelligent biological prediction, and particularly relates to an RNA-small molecule binding affinity prediction method based on multi-view learning. The method comprises three stages of data set up and down sampling processing, feature construction and extraction based on RNA and small molecule sequences, and binding affinity prediction. According to the method, data set distribution is optimized through an up-down sampling method, multi-view feature information is constructed through sequence information of RNA and small molecules, a deep network is established to extract and depth biological information features, and finally, an MLP regression device is adopted to predict an RNA-small molecule binding affinity value, so that drug discovery work is assisted to be achieved. In order to solve the problem of imbalance of the existing data set, the invention provides a method of combining up and down sampling for processing, and the problem of imbalance is effectively relieved.

The application discloses a pathogenic Vibrio Pir B virulence protein binding peptide P2 and application thereof. The small-molecule binding peptide P2 has high affinity with the Pir B virulence protein and has an amino acid sequence of LGSPLLTYGRPQ. The application screens the binding peptide with high affinity with the pathogenic Vibrio Pir B virulence protein from a random peptide library through phage display technology, and the binding peptide is chemically synthesized. After injection of the binding peptide, the survival rate of shrimps after infection with Vibrio can be effectively improved, and the shrimps have a remarkable protection effect in shrimp culture. The binding peptide can efficiently bind to the pathogenic Vibrio Pir B virulence protein, and effectively reduce the virulence of the Pir B protein. In addition, the method can effectively reduce the use of antibiotics in healthy shrimp culture, reduce the generation of drug-resistant strains, and has a good application prospect in the prevention and treatment of shrimp AHPND.

The application discloses a kind of RNA small molecule binding site prediction method based on multiscale geometric deep learning, belong to bioinformatics and structural biological computing field.The method obtains RNA-small molecule complex structure data and constructs residue level binding site label, extracts RNA sequence information and atomic three-dimensional structure features, generates sequence representation using pre-training RNA language model, constructs deep learning model including hybrid atom encoder, attention type atom to residue polymerization module, residue level space graph neural network module and geometric bias global attention module, fuses atomic level, residue level and global multiscale information, carries out binding site prediction to RNA residue, outputs binding probability and prediction uncertainty.The method can improve prediction accuracy and generalization ability, and is suitable for RNA target drug design and structure-guided small molecule screening.

The present disclosure relates to compounds and compositions, and methods of uing the compounds and compositions for inducing the degradation of proteins that are relevant to cancer such as. for example. KDM4B and VCL. Also described are methods of treating cancer (e.g, a sarcoma, a carcinoma, a hematological cancer, a solid tumor, breast cancer, cervical cancer, gastrointestinal cancer, colorectal cancer, brain cancer, skin cancer, prostate cancer, ovarian cancer, non-small cell lung carcinoma, thyroid cancer, testicular cancer, pancreatic cancer, liver cancer, endometrial cancer, melanoma, glioma, leukemia, lymphoma, chronic myeloproliferative disorder, myelodysplastic syndrome, myeloproliferative neoplasm, plasma cell neoplasm (myeloma)) using the disclosed compounds and compositions. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present disclosure.