188 results about "Binding affinities" patented technology

The embodiment of the invention provides a drug optimization method and system based on the overall effect of a protein network. The method comprises the following steps: constructing a protein interaction network related to a target disease, and dividing each protein target into a risk protein set and a protection protein set; respectively calculating first binding affinity data of the candidate drugs and each protein target in the risk protein set, and generating a first network comprehensive score based on the first binding affinity data; respectively calculating second binding affinity data of the candidate drugs and each protein target in the protection protein set, and generating a second network comprehensive score based on the second binding affinity data; calculating network confrontation scores of the candidate drugs according to the first network comprehensive score and the second network comprehensive score; and determining whether the candidate drug is a preferred drug based on the network adversarial score. The method can overcome the defect that a single-target drug is insufficient in curative effect due to a network compensation effect, so that safer and more effective candidate drugs are screened out.

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 invention relates to the technical field of biological medicines, in particular to a preparation method of an inhibitor targeting a MAX-PD-L1 promoter specific binding motif and a double-target inhibitor, through ChIP-seq and site-directed mutagenesis experiments, a core binding motif of MAX and a PD-L1 promoter, such as 5 '-CAC [GA] TG-3', is defined, it is ensured that the inhibitor only targets a key site of MAX-PD-L1 interaction, and the activity of the MAX-PD-L1 promoter specific binding motif is improved. The off-target effect is avoided, and a high-specificity target spot is provided for subsequent inhibitor design. The cell permeability of the DNA aptamer screened based on the specific binding motif is improved after cholesterol modification, and the affinity of the DNA aptamer is obviously higher than that of a traditional antibody. A small molecule compound virtually screened through a molecular docking model is optimized through hydrogen bond and hydrophobic interaction, and then the binding affinity with MAX is improved. After treatment with the inhibitor, the combination inhibition rate of MAX and the PD-L1 promoter is high, the transcriptional activity of PD-L1 is obviously reduced, the killing rate of T cells to tumor cells is also improved, and immune escape is effectively blocked.

Mutations in oncogenes and tumor suppressor factors contribute to the development and progression of cancer. This disclosure describes compounds and methods for restoring DNA-binding affinity of p53 mutants, as well as their use in diagnostic assays to guide the treatment of subjects with said compounds for cancer. The compounds of this disclosure can bind to mutant p53 and restore the ability of p53 mutants to bind to DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers containing p53 mutations.

The disclosure provides aptamer switch polynucleotides whose kinetics and effective binding affinity to a target analyte can be independently tuned. The aptamer switch polynucleotides comprise an aptamer, an intramolecular linker, and a displacement strand.

The application relates to the technical field of computer-aided drug design, and provides a molecule generation method, system, medium and equipment for drug discovery, which comprises the following steps: acquiring a SMILES string of a ligand and an amino acid sequence of a target protein, respectively extracting a ligand feature vector and a protein feature vector, splicing and fusing, and then predicting a binding affinity value through a multilayer perception machine; taking the protein feature vector as a condition, generating a new molecular potential representation through a reverse denoising process of a conditional diffusion model; wherein, at each step of the reverse denoising process, a graph-level readout operation is performed on pure noise, an affinity value is predicted through the multilayer perception machine, a gradient of an affinity guidance loss is returned to a noise prediction network, and the new molecule generation is guided to a high affinity area; and the new molecular potential representation is decoded into a SMILES string through a pre-trained molecular language decoder. Novel molecules with high binding potential can be quickly generated.

The present application provides a polypeptide as CDRs in an antibody light chain, light chain variable region or light chain, which is capable of constructing an antibody with CDRs in an antibody heavy chain, heavy chain variable region or heavy chain having binding affinity and / or specificity to different target proteins (antigens), the antibody retaining binding affinity and / or specificity to the target proteins (antigens) and biological activity. The present application also provides an anti-B7-H3 and / or EGFR antibody comprising the polypeptide as a light chain variable region or light chain.

A method and an apparatus for predicting a target protein-based toxicity value are disclosed. The method for predicting a toxicity value, according to one embodiment of the present invention, may comprise the steps of: receiving target protein structure information, compound structure information, and toxicity information; predicting binding affinity on the basis of the received target protein structure information and compound structure information; acquiring compound feature information from the received compound structure information by means of a meta-ensemble method; predicting a toxicity value by concatenating results obtained by learning the predicted binding affinity and the toxicity information through each one of a fully connected layer and a graph convolutional layer according to a method forming the meta-ensemble method; analyzing the effect of detailed fragments forming a compound on the toxicity value when the predicted toxicity value is greater than or equal to a preset value; and using the analyzed effect to determine a detailed fragment to be maintained when a new compound is generated among the detailed fragments.

Fully human monoclonal Abs includes (i) an antigen-binding variable region that exhibits very high binding affinity for IL-1α and (ii) a constant region that is effective at both activating the complement system though C1q binding and binding to several different Fc receptors.

The invention discloses a method for preparing a VA-ECMO lung injury treatment medicine by using ginkgolide A to regulate YARS1, and relates to the technical field of biological medicine, the method comprises the following steps: by using ginkgolide A as a YARS1 protein regulator, preparing the medicine for treating the VA-ECMO lung injury through virtual screening, binding affinity confirmation and cell efficacy confirmation; wherein the virtual screening is based on a protein structure model of YARS1, and bilobalide A with high affinity binding energy with YARS1 is screened out through molecular docking. It is proved that ginkgolide A can effectively improve the lung ventilation function by regulating YARS1, repair the alveolar epithelial barrier structure and inhibit the inflammatory oxidative stress reaction, and the lung injury treatment effect and clinical transformation safety under the support of VA-ECMO are improved.

A fusion protein comprising at least one first polypeptide moiety and at least one second polypeptide moiety wherein the first polypeptide moiety is a single-chain polypeptide capable of binding to a target entity and the second polypeptide moiety is a stabilizing polypeptide and comprises a single-chain alpha-helix-containing domain, wherein the second polypeptide moiety has no binding affinity for the target entity. The presence of the second polypeptide moiety may improve at least one property of the fusion protein as compared to the property of the first polypeptide moiety alone, where the improved property is selected from the group consisting of: alkaline stability, recombinant protein expression, and coupling to a vector.

The present invention relates to a method for producing antibodies with an increased plasma half-life comprising the steps of (i) producing an antibody in a culture of Phaeodactylum tricornutum, (ii) purifying said antibody and (iii) determining the binding affinity of said antibody for the FcRn receptor.

The present disclosure relates to a class of polypeptides derived from Staphylococcus Protein A (SpA) or any domain thereof, that exhibit an improved binding affinity for IgA. Moreover, IgA binding polypeptides that selectively bind IgA among other immunoglobulin isotypes are also provided. The present disclosure also relates to methods for isolating IgA, such as antibodies of isotype IgA, using said polypeptides as well as related products, such as separation matrices coupled to said IgA binding polypeptides and / or multimers thereof.

An aptamer composition is disclosed which has one or more oligonucleotides that include at least one of deoxyribonucleotides, ribonucleotides, derivatives of deoxyribonucleotides, derivatives of ribonucleotides, or mixtures thereof. The aptamer composition has a binding affinity for one or more cellular membrane glycoproteins selected from the group consisting of: intercellular adhesion molecule 1 (ICAM-1), low-density lipoprotein receptor (LDLR) family members, and cadherin-related family member 3 (CDHR3), preferably intercellular adhesion molecule 1 (ICAM-1), and is configured to reduce the binding of one or more human rhinoviruses to the intercellular adhesion molecule 1 (ICAM-1).

Polypeptides are provided for use as antibody light chains or light chain variable regions. These polypeptides can be used to construct antibodies with antibody heavy chains or antibody heavy chain variable regions that have binding affinity for different targets (antigens), and the antibodies retain their binding affinity and biological activity for the targets (antigens). Furthermore, antibodies comprising these polypeptides are provided.

This invention provides a simple method for evaluating whether or not a peptide binds to isovaleric acid. [Solution] A method for evaluating the binding affinity to isovaleric acid, comprising a preparation step of preparing a fluorescently labeled compound in which a fluorescent group is bonded to the α-carbon atom of isovaleric acid, and a contact step of contacting the fluorescently labeled compound with a peptide fragment of an olfactory receptor.

The present application relates to the field of biological medicine and clinical diagnosis, and more particularly, the present application relates to a polypeptide having binding affinity to AXL protein and application thereof; the polypeptide has binding affinity to AXL protein, and therefore can be used for detecting AXL protein, so that the polypeptide has diagnostic or therapeutic use as a drug or molecular targeting reagent.

The present application relates to a kind of based on chemotactic factor CXCL12 mutant modification double specific fusion protein and its application as immune checkpoint molecule targeted degradation platform in tumor immunotherapy, belong to biological medicine field.The specific problem of the present application is how to effectively enhance the effect of tumor immunotherapy, especially solve the problem of immune escape phenomenon in tumor microenvironment in traditional immunotherapy.To this end, the present application proposes a new KineTAC targeted degradation platform, specifically designs a new chemotactic factor CXCL12 and target protein binding polypeptide (such as anti-PD-1 / PD-L1 monoclonal antibody, anti-LAG-3 monoclonal antibody, etc.) Fusion expression protein molecule, enhance its binding affinity with receptor CXCR4 and CXCR7, and avoid stimulating tumor cell growth proliferation.The fusion protein can target and degrade the immunosuppressive molecules on the surface of tumor cells and immune cells, thereby enhancing the immune response of immune cells and improving the anti-tumor effect.

This invention belongs to the field of biotechnology, providing a mouse anti-human ELL2 monoclonal antibody, its preparation method, and its applications. This invention successfully obtained a 2E1 anti-human ELL2 monoclonal antibody and established a hybridoma cell line capable of stably producing this antibody. The binding affinity (KD) of the obtained 2E1 monoclonal antibody to human ELL2 protein reached the picomolar level (approximately 10^-3 kDa). ‑12 The antibody (M) exhibits extremely strong binding ability. Cross-reactivity tests confirmed that it binds only to human ELL2, and shows no binding signal with highly homologous human ELL1, ELL3, and mouse ELL2, thus completely solving the specificity problem of existing technologies.

The present disclosure provides a scaffold comprising a heterologous moiety and Spirulina spp. That expresses the scaffold. Also provided are recombinant Spirulina expressing the scaffolds and methods of treating diseases and conditions using the same. Homologous and heterologous scaffolds comprising VHH antibodies linked by modified smAKAP linkers can be used to increase binding affinity as compared to VHH antibodies alone.

Provided herein are compositions of chimeric shuttle-binder-effector fusion proteins with components related to modulating endogenous cytotoxic effector mechanisms, which are useful for therapeutic effects on predetermined target molecules. These shuttle-binder-effector proteins also have specific epitope binding affinities for these target molecules. Compositions for modified cells expressing these chimeric shuttle-binder-effector fusion proteins are also provided. Methods for the modification of cells to express these chimeric shuttle-binder-effector fusion proteins and for delivering the chimeric shuttle-binder-effector fusion proteins into target cells using the lytic granule cellular mechanisms in these modified cells are also provided.

A deep learning-based method for predicting HLA-I binding to TCRs is proposed. This method collects comprehensive peptide-TCR binding records from four databases: IEDB, VDJdb, PIRD, and McPas-TCR, forming a dataset. The steps include: preprocessing the data before inputting it into the model to obtain a one-hot encoding matrix; inputting the one-hot encoding matrix into a deep learning model for learning, and predicting the binding probability. This invention can efficiently and accurately predict the binding affinity between TCRs and HLA-I complexes and requires only the CDR3β sequence.

This invention relates to a pufferfish TRPV1 inhibitory peptide, its preparation method, and its application. The amino acid sequence of the peptide is LDIF. The preparation method includes: 1. Enzymatically hydrolyzing pufferfish skin, then inactivating the enzyme, and screening for peptides with a molecular weight not greater than 1 kDa from the hydrolysate, followed by freeze-drying to obtain the pufferfish skin enzymatic hydrolysate peptide; 2. Performing mass spectrometry analysis on the pufferfish skin enzymatic hydrolysate peptide, using mass spectrometry analysis software, and selecting multiple non-repeating peptide sequences based on the criteria of confidence level -10lgP > 20 and amino acid count < 10; 3. Molecularly docking the selected peptide sequences with the TRPV1 receptor using software to select peptide sequences with strong binding affinity to the TRPV1 receptor; 4. Solid-phase synthesis of the selected peptide sequences to obtain the peptide LDIF. This invention uses pufferfish skin as raw material to obtain a peptide with good inhibitory effect on TRPV1, which can be used to prepare skin care products for soothing sensitive skin.

The present invention provides an antibody or antigen-binding portion thereof that can bind to properdin (factor P). The antibody of the current invention leads to selective inhibition of alternative complement pathway while allowing the classical and lectin pathways to continue. Further, the antibody of the present invention may have modified or reduced binding to FcγRs to minimize its ADCC activity. The present invention provide an antibody that comprises an amino acid sequence to minimise its CDC activity. The antibody according to the present invention has higher FcRn binding affinity and therefore the antibody according to the present invention may have long circulating half-life in the body of the patient and it can be given at a reduced dosing frequency. The antibody according to the present invention can further be used in the preparation of a drug for treating diseases through inhibition of alternative complement pathway.

Provided herein are affinity matured anti-galectin-9 (Gal9) antibodies. The antibodies have improved binding affinity to Gal9. Also provided herein are method of use of the affinity matured anti-Gal9 antibodies, including methods of treatment of cancer, methods of rescuing or promoting effector T cell proliferation, methods of enhancing effector T cell activity, and / or of identifying and treating cancer in a subject including the administration of the anti-Gal9 antibodies described herein. Also provided are polynucleotides encoding the heavy chain or the light chain or the antigen-binding portion thereof described herein, and vectors, especially expression vectors, including the polynucleotides described herein.

Embodiments of the disclosure involve modeling DEL data using factorized molecular representations (e.g., hierarchical mono-synthon and di-synthon building blocks), which capitalizes on the inherent hierarchical structure of these molecules. Using the factorized molecular representations, machine learning models are trained to learn latent binding affinity of compounds for targets and one or more covariates (e.g., load / replicate noise). This leads to improved predictions by the machine learning models in the form of higher enrichment scores, which are well-correlated with compound-target binding affinity.

The present invention relates to a mutant protein of a single-chain variable fragment having improved stability and, more specifically, to a mutant protein of a single-chain variable fragment having excellent binding affinity to immune checkpoint molecules and superior in vivo stability, in which a heavy-chain variable region including CDRH1 of SEQ ID NO: 1, CDRH2 of SEQ ID NO: 2, and CDRH3 of SEQ ID NO: 3 and a light-chain variable region including CDRL1 of SEQ ID NO: 4, CDRL2 of SEQ ID NO: 5, and CDRL3 of SEQ ID NO: 6 are linked by a stability-enhancing linker of SEQ ID NO: 7.

Provided herein are computer-implemented methods for scoring a binding affinity between molecular subsystems. The methods include representing an interaction structure of the molecular subsystems, calculating the molecular interactions between the molecular subsystems, and generating an interaction energy score between the molecular subsystems.

Various aspects of the present disclosure relate to techniques for computational target identification and validation. An apparatus is configured to determine protein structure data associated with a plurality of genes, wherein the protein structure data describes one or more protein structures, simulate interactions between a plurality of compounds and the one or more protein structures, determine binding affinities between each of the plurality of compounds and the one or more protein structures, and generate a list of validated or novel targets based on the binding affinities.

The application discloses a polypeptide with binding affinity to IL-6 and application thereof. The amino acid sequence of the polypeptide comprises one or more of sequences shown in SEQ ID NO. 1-6. The application obtains the polypeptide with affinity to IL-6 through screening, which can specifically bind to IL-6, so that IL-6 is enriched, and then IL-6 is adsorbed at an inflammation infection site, thereby providing more choices for treatment of diseases related to removal of inflammatory factors and IL-6 overabundance, and the polypeptide can be used for IL-6 detection and preparation of drugs for targeted binding to IL-6 or treatment of diseases related to IL-6.