225 results about "Target binding" patented technology

The invention provides a drug target binding affinity prediction method based on multi-modal data fusion. The method comprises the following steps: firstly, extracting sequence feature information of drug SMILES and target FASTA, then constructing an affinity graph, modeling drug molecules and target protein molecules into an undirected graph, and extracting molecular-level features of atoms, bonds, residues and contact. And fusing the hierarchical graph structure information of the affinity graph and the molecular graph to obtain the graph structure feature representation of the drug-target spot. The sequence feature information and the graph structure feature representation are further fused by using intramolecular and intermolecular attention fusion mechanisms. And finally, performing affinity prediction by using the fused features, and outputting a drug-target binding affinity score. According to the method, sequence and structural information are effectively fused, the accuracy of drug target affinity prediction is improved, and the problems of insufficient information fusion and insufficient structural information utilization in an existing method are solved.

The present disclosure provides in some embodiments, a multi -objective binder design framework by aligning autoregressive molecular foundation models (e.g., protein language models (pLMs)) to different objectives, such as binding and developability considerations. In some embodiments, direct preference optimization (DPO) can be utilized in the methods and systems described herein to encode multiple design objectives in the language model through direct optimization on expert curated preference sequence datasets comprising preferred and dispreferred distributions. In some embodiments, utilizing the described framework can enable molecular foundation models (e.g., protein language models), such as ProtGPT2, to effectively design binders conditioned on specified receptors and one or more drug developability criteria. Besides being multi -objective, in some embodiments, the methods and systems provided herein conceive online lab-in-the-loop design pipelines by actively incorporating experimental feedback.

A query-based generic end-to-end molecular optimization (“QMO”) system framework, method and computer program product for optimizing molecules, such as for accelerating drug discovery. The QMO framework decouples representation learning and guided search and applies to any plug-in encoder-decoder with continuous latent representations. QMO framework directly incorporates evaluations based on chemical modeling, analysis packages, and pre-trained machine-learned prediction models for efficient molecule optimization using a query-based guided search method based on zeroth order optimization. The QMO features efficient guided search with molecular property evaluations and constraints obtained using the predictive models and chemical modeling and analysis packages. QMO tasks include optimizing drug-likeness and penalized log P scores with similarity constraints and improving the target binding affinity of existing drugs to pathogens such as the SARS-CoV-2 main protease protein while preserving the desired drug properties. QMO tasks further improves optimizing antimicrobial peptides toward lower toxicity.

The invention discloses a leukemia targeted therapy preparation as well as a preparation method and application thereof. Comprising a DNA nanoflower carrier targeting leukemia cells through a PTK7 receptor and benzene arsenic oxide loaded on the carrier. The DNA nanoflower carrier is obtained by rolling circle amplification, and a nucleic acid aptamer complementary sequence of targeted binding leukemia cells is introduced into a template chain subjected to rolling circle amplification. The preparation method comprises the following steps: modifying sulfydryl onto a DNA nanoflower by using DNA-Dithiol, then breaking a disulfide bond by using reduced glutathione to expose the sulfydryl, and loading benzene arsenic oxide onto the DNA nanoflower through a reaction between trivalent arsenic and the sulfydryl. The structure of the DNA nanoflower has a high surface area and high porosity, and can load a large amount of PAO, so that the killing performance on cancer cells is enhanced; the aptamer sgc8 sequence is introduced into the DNA nanoflower, so that the targeting of the DNA nanoflower to cancer cells is effectively realized; the preparation also has the advantages of being good in thermodynamic stability, easy to store, excellent in biocompatibility and the like, and has a very good application prospect.

The invention discloses a compound-target binding affinity prediction method based on multi-modal feature fusion, and relates to the technical field of compound activity prediction, and the technical key point is that the method comprises the steps of data acquisition, multi-modal feature characterization, multi-modal feature extraction and fusion, and affinity prediction to predict the compound activity. The problems of long time consumption, high cost, low efficiency and the like of compound activity prediction are solved through assistance of an artificial intelligence algorithm, and information can be processed in parallel in a self-adaptive and self-learning manner by referring to a multi-layered structure of a human brain and a layer-by-layer analysis processing mechanism of neuron information interaction. The intensity information of the interaction between the compound-target pair is provided by combining the affinity, the affinity between the compound and the target is predicted through a deep learning method, and the specific biological activity and key action target of the compound are analyzed.

The invention discloses a resource binding method, electronic equipment and a storage medium. The method comprises the steps that in response to an interrupt request to be processed of a target instance, a target binding strategy is determined, and the target binding strategy is used for determining that a network card interface corresponding to the interrupt request and processor resources to be bound with the interrupt request are located in the same resource node of a processor architecture; and carrying out resource binding processing on the interrupt request according to the target binding strategy to obtain a binding processing result. The technical problem of poor network performance caused by sequential binding of processor resources only according to the interrupt number in the prior art is solved.

The invention relates to the technical field of bioinformatics and artificial intelligence, and provides a drug-target interaction prediction method and system based on multi-modal feature fusion, and the method comprises the steps: carrying out the word segmentation coding of an obtained to-be-recognized drug sequence and a target sequence, and respectively extracting the subsequence features of a drug and a target; constructing a two-dimensional molecular diagram of the drug and a three-dimensional structure diagram of the target, and respectively extracting diagram structure characteristics of the drug and the target; fusing the subsequence features and graph structure features of the drug and the target through a cross attention mechanism; and carrying out interactive fusion by adopting a bidirectional collaborative attention mechanism to obtain a prediction result of the binding affinity of the drug and the target. According to the invention, by combining the multi-modal complementary information of the drug and the target, deep interaction between different modal features is deeply mined; meanwhile, a two-way collaborative attention mechanism is introduced into interaction modeling of the drug and the target, and the accuracy of drug-target binding affinity prediction is effectively improved.

The invention discloses a fusion protein taking peptide-N-glycosidase as an active component as well as a preparation method and application of the fusion protein, and belongs to the technical field of biological medicines. The fusion protein comprises: (a) peptide-N-glycosidase or a catalytically active fragment thereof; (b) an immunoglobulin Fc domain, or a combination of a tumor or immune cell antigen binding domain and an immunoglobulin Fc domain; (c) a linker peptide; wherein the form of the tumor or immune cell antigen binding domain is Fab, scFv or VHH; the peptide-N-glycosidase or the catalytic activity fragment of the peptide-N-glycosidase is connected with the Fc structural domain of the immunoglobulin through the connecting peptide; the immunoglobulin Fc domain mediates the fusion protein to form a homodimer or a heterodimer. According to the invention, the synergistic function of targeted binding and local deglycosylation of the target molecule is realized, so that the immunosuppressive activity of the target molecule is interfered, and the anti-tumor immune response is enhanced.

The present disclosure provides a polypeptide complex comprising a target binding polypeptide that binds to a molecule on a target cell or a molecule in an extracellular matrix (ECM); and small latent complexes comprising in particular a dimer latent related polypeptide (LAP) or a fragment or derivative thereof, and a dimer mature transforming growth factor beta (TGF beta) family polypeptide or a fragment or derivative thereof. Polypeptides (e.g., fusion polypeptides), and related polynucleotides, vectors, cells, and pharmaceutical compositions are also provided. Also provided are methods of treating subjects using, for example, these polypeptide complexes and / or these fusion polypeptides or pharmaceutical compositions thereof.

Embodiments of the present disclosure relate to modeling DEL data using factorized molecular representations (e.g., hierarchical single and double synthon building blocks), which leverages the hierarchical structure inherent to these molecules. Using factorized molecular representations, machine learning models are trained to learn the underlying binding affinity of compounds to targets and one or more covariates (e.g., loading / repeat noise). This results in machine learning models producing improved predictions in the form of higher enrichment scores that have good correlation with compound-target binding affinity.

The present invention relates to humanized antibodies or target-binding fragments or derivatives thereof retaining target binding capacities, which bind to human iRhom2 (FIG. 1).

The disclosure relates generally to electrodes with a target-binding molecule conjugated on its surface that is overlaid with a polymer of sufficient thickness to restrict ion mobility so that the electrical double layer is moved closer to the site of target binding to the immobilized target-binding molecule. Generally, thickness of the polymer coating layer is such that a target-binding site of the immobilized target-binding molecule is not in the coating layer, e.g., the target-binding site is exposed. The disclosure also provides sensors comprising the electrode and uses of the electrodes and sensors in target analyte detection, e.g., in label-free detection of targets. WO

The invention discloses a 5-bromoindole-2-carboxylic acid methyl ester derivative as well as a preparation method and application thereof in a protein inhibitor, and relates to the technical field of synthesis and preparation of inhibitors. According to the 5-bromoindole-2-carboxylic acid methyl ester derivative, compared with a contrast product, the synthetic route steps of the prepared 5-bromoindole-2-carboxylic acid methyl ester derivative are simpler and more convenient, structural modification and preparation are easier, the application range of a substrate is widened, the yield of the product is increased, and the yield of the product is increased. The differentiated requirements on the molecular structure novelty in the field of kinase inhibitors can be met. An epidermal growth factor receptor (EGFR) inhibitor prepared from the 5-bromoindole-2-carboxylic acid methyl ester derivative is higher in inhibition efficiency on biological activity, the physiological solubility is improved more remarkably, a more excellent and stable target binding result can be shown, and the EGFR inhibitor can be used for preparing an epidermal growth factor receptor (EGFR) inhibitor. The application effect of the compound in scenes such as antitumor drug development and the like is favorably improved.

This invention discloses a KK-LC-1 targeting binding protein and its derivatives, a kit, and applications. The protein sequence of the KK-LC-1 targeting binding protein is shown in one of SEQ ID No. 2, SEQ ID No. 3, SEQ ID No. 4, and SEQ ID No. 5. The KK-LC-1 targeting binding protein of this invention has a molecular weight of only about 17 kDa, approximately one-tenth that of an antibody, exhibiting good tissue penetration. Furthermore, its production process is simple and yields high quantities. The targeting binding protein of this invention demonstrates good targeting activity against KK-LC-1-positive tumors both in vivo and in vitro, and can be used for targeted tumor drug delivery, representing a potential drug for tumor immunotherapy. Simultaneously, a KK-LC-1 serum detection kit was developed using the targeting binding protein, enabling quantitative detection of KK-LC-1 levels in the human body.

The present disclosure provides recruitment of a ULK initiation complex (e.g., a ULK1 initiation complex) used to induce selective autophagy, a process by which the degradative mechanism is targeted to specific substrates. Chimeric compounds for binding to the ULK initiation complex, comprising a ULK complex binding moiety, a linker, and a target binding moiety, are provided, as well as a target of interest.

The application discloses use of LncRNA00_178, miR-466b-3p and Gucy1b1 as acute lung injury markers or drug targets, and belongs to the technical field of biomarkers and drug targets. LncRNA00_178 can be used as a biomarker for screening or diagnosing acute lung injury, a miR-466b-3p down-regulator can be used to prepare a pharmaceutical composition for preventing and treating acute lung injury, and Gucy1b1 can be used as a drug target to prepare a drug for preventing and / or treating acute lung injury. The application has the beneficial effects that the application proposes that LncRNA00_178 and miR-466b-3p, and miR-466b-3p and Gucy1b1 have a target binding relationship. LncRNA00_178 can be used as a biomarker for screening or diagnosing acute lung injury, the silence of miR-466b-3p inhibits LPS-induced apoptosis of alveolar epithelial cells, and Gucy1b1 can be used as a drug target to prepare a drug for preventing and / or treating acute lung injury. The data provide new insights for the treatment mechanism of ALI and the identification of specific targets, and provide a new idea for the research and development of new drugs for acute lung injury, and have a wide application prospect.

The present disclosure addresses the problem of providing technology for phagocytizing unwanted cells or the like in vivo.　This protein includes, from the N-terminus to the C-terminus, (A) a target binding region that binds to a target, and (C) an SHBG-like domain of ProS.

The invention discloses equipment for binding a planar target material and a binding method thereof.The equipment for binding the planar target material comprises a workbench, a set of downward pressing assemblies are symmetrically arranged on the two sides of the upper portion of the workbench, each downward pressing assembly comprises a lifting driving mechanism and a downward pressing disc, and each downward pressing disc is downwards provided with a pressing disc through an elastic piece; a plurality of adsorption holes are evenly distributed in the pressing disc, and the bottom side of the lower pressing disc is fixedly connected with a jacking piece downwards. The negative pressure pumping mechanism comprises a negative pressure pumping hole formed in the jacking piece in a penetrating mode, the negative pressure pumping hole is connected to a negative pressure pumping pipe through a corresponding parallel pipe fitting, and the negative pressure pumping pipe is connected with a pressure relief pipe; and the heating mechanism comprises a driving piece, the driving piece is rotationally driven by a corresponding heating driving mechanism, and a heater capable of switching positions below the two sides of the workbench is rotationally installed on the upper portion of the driving piece. The operation convenience of plane target material binding can be effectively improved, and the binding bonding rate of the target material can be effectively improved.

The present invention discloses a method for screening effective substances of traditional Chinese medicine based on a 6-dimensional spider web model, belonging to the field of medical technology. Based on the results of UHPLC analysis, the present invention uses danshensu, chlorogenic acid, procyanidin B2, epicatechin, hyperoside, isoquercetin, rosmarinic acid, lithospermic acid, salvianolic acid B, salvianolic acid A, dihydrotanshinone I, tanshinone I, cryptotanshinone, tanshinone IIA, oleanolic acid, and ursolic acid as the "specific" candidate effective ingredients of the Danshen-Hawthorn medicinal pair. Based on the data of the candidate effective ingredients in six dimensions, namely, effectiveness dimension, compatibility environment dimension, transmission and traceability dimension, content measurability dimension, network pharmacology degree value dimension, and molecular docking target binding activity dimension, a "spider web" model is constructed to obtain the key effective substances of the Danshen-Hawthorn medicinal pair. The present invention provides theoretical support for revealing the compatibility theory of the Danshen-Hawthorn medicinal pair, formulating its quality evaluation standards, and clinical application of the Danshen-Hawthorn medicinal pair.

The present invention relates to humanized nanobodies targeting cadherin 17 and their applications, and to the technical fields of immunology and molecular biology. The complementary determining region of the humanized nanobody includes a CDR1 with an amino acid sequence as shown in SEQ ID NO: 2, a CDR2 with an amino acid sequence as shown in SEQ ID NO: 4, and a CDR3 with an amino acid sequence as shown in SEQ ID NO: 6; the framework region of the humanized nanobody includes a FR1 with an amino acid sequence as shown in any one of SEQ ID NO: 1 and SEQ ID NO: 8, an FR2 with an amino acid sequence as shown in any one of SEQ ID NO: 3, SEQ ID NO: 9, and SEQ ID NO: 11, an FR3 with an amino acid sequence as shown in any one of SEQ ID NO: 5 and SEQ ID NO: 10, and an FR4 with an amino acid sequence as shown in SEQ ID NO: 7. The humanized nanobody of the present invention reduces the immunogenicity of the nanobody, improves the target binding activity and killing activity, and can be used to develop immune detection reagents, CAR-T / NK cell drugs, and antibody drugs.

Disclosed herein are methods and compositions for detecting (+)-methamphetamine using dye-complexed and redox-tag-labeled aptamers that generate a detectable signal upon target binding.

Macromolecule compositions and related methods that effect targeted delivery of therapeutic agents to effector targets in a desired cell, tissue and / or organ of interest while minimizing or avoiding undesirable delivery to other cells, tissues or organs are provided. Compositions and methods related to macromolecules, such as an ANDbody™, that include an effector target binding domain specific for an effector target, and an address binding domain specific for an address target are described. The macromolecules are linked to small molecules.

Described in several example embodiments herein are engineered bifunctional receptors that can include an E3 ligase binding domain and a target binding domain operatively coupled to the E3 ligase binding domain. In some embodiments, the engineered bifunctional receptors are capable of targeted degradation of a target protein. Also described in several example embodiments herein are compositions, formulations, and cells that can include or generate the engineered bifunctional receptors and uses thereof.

The invention discloses a eukaryotic protein for targeted binding and degradation of HIF-1alpha as well as a preparation method and application of the eukaryotic protein, and belongs to the field of medical bioengineering, the full length of the protein is 189 amino acids, the protein has an amino acid sequence as shown in SEQ ID No.1, a corresponding base sequence is as shown in SEQ ID No.2, and the protein is derived from 560th-748th amino acids of a gene DTX3L and covers RING and CTD functional domains of DTX3L protein. The HIF-1alpha protein is modified through ubiquitination, degradation of the HIF-1alpha protein is promoted, the activity of the HIF-1alpha protein is reduced, the defects that existing targeted inhibitors, RNA interference, antisense oligonucleotides, bait oligonucleotides and the like are low in safety and not obvious in curative effect are overcome, the protein level of the HIF-1alpha in cells can be reduced, and the treatment effect of the HIF-1alpha is improved. The preparation method is beneficial to treatment of HIF-1alpha related diseases such as tumors, rheumatoid arthritis and inflammatory bowel diseases.

Provided herein are compounds, pharmaceutical compositions, and methods for binding or degrading target proteins. Further provided herein are bifunctional compounds having a DNA damage-binding protein 1 (DDB 1) binding moiety, a linker, and a target binding moiety.

The invention discloses application of a cacumen biotae extract in activating Nrf2 protein in cells, and particularly relates to the field of cosmetics. Wherein the activation of the Nrf2 protein in the cell is realized by interrupting the Keap1-Nrf2 protein-protein interaction in the cell, and performing targeted combination with the Keap1 protein and releasing the Nrf2 protein. By activating the Nrf2 pathway, the Chinese arborvitae twig and leaf extract can simultaneously achieve anti-oxidation, anti-inflammatory, anti-aging and whitening effects, and meets the requirements of cosmetics for multi-target effects.

The invention belongs to the technical field of biological medicine, and particularly relates to a DLL3 targeted binding protein and application. The DLL3 targeted binding protein has an amino acid sequence as shown in SEQ ID NO. 1, SEQ ID NO. 2 or SEQ ID NO. 3. The DLL3 targeted binding protein disclosed by the invention can be specifically bound with DLL3, the binding affinity reaches nM level, the molecular weight is about 18kDa which is far less than that of a traditional antibody molecule, and the DLL3 targeted binding protein has stronger tissue penetrability and lower immunogenicity. Related tests show that the DLL3 targeted binding protein disclosed by the invention can be used for diagnosis, treatment and drug delivery of DLL3 positive tumors, and has a wide clinical application prospect.

The invention discloses a small molecular probe for targeting a mutant EGFR (Epidermal Growth Factor Receptor). The small molecular probe comprises an EGFR targeting binding group and a fluorophore. The micromolecular probe can be used for imaging diagnosis of EGFR mutant tumors, can also be used for targeted therapy, and has an important clinical application prospect.

This application discloses a method, apparatus, and computer device for evaluating ligand binding sites in a complex. The method involves binding a target ligand to multiple candidate binding sites within a target protein, obtaining a candidate complex conformation corresponding to each candidate binding site; acquiring distance information between each atom of the target protein and each atom of the target ligand in each candidate complex conformation; determining the binding strength information between the target protein and the target ligand in each candidate complex conformation based on the distance information; and determining the target binding site based on the binding strength information. This method can improve the accuracy of ligand binding site evaluation in complexes.

A peptide or a derivative thereof or a salt thereof, including a hydrophobic region, and a hydrophilic region positioned on at least one end side of the hydrophobic region and having hydrophobicity lower than that of the hydrophobic region, including, at one end, a first target binding site capable of binding to a first target, and including, at the other end, a second target binding site capable of binding to a second target. The peptide is applicable to an active targeting DDS.