328 results about "Binding affinities" patented technology

The invention provides an anti-cancer active component optimization method for breast cancer treatment, which comprises the following steps: analyzing a potential interference path of an anti-cancer active component on immune system cell viability by adopting a computational chemistry simulation method according to a preliminary structural function mapping relationship, and determining a specific molecular mechanism range of immune system weakening; according to the synergistic effect evaluation result, optimizing the structural parameters of the active components through a molecular docking algorithm, adjusting the binding affinity of the active components with tumor cell targets and pathogenic bacteria targets, and determining a final structural optimization scheme; aiming at the final structure optimization scheme, verifying the expression of the modified active component on tumor inhibition and antibacterial ability by adopting simulation data of an in-vitro activity test, and obtaining a verification data set of comprehensive performance; and aiming at the updated active component design data, through a multi-objective optimization model, balancing the synergism of an anti-cancer effect and a health protection mechanism, and determining a final compound structure configuration suitable for complex requirements of a clinical environment.

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 provides an application of polyphyllin VII in preparation of an Akt signaling pathway inhibitor targeting GRB2, the invention reveals that PPVII is specifically combined with GRB2 protein and regulates and controls the function of the GRB2 protein for the first time, the Akt pathway inhibition effect is exerted, and the molecular mechanism of PPVII is specifically shown as follows: molecular docking and dynamic simulation confirms that PPVII and an SH3 structural domain of GRB2 form a stable compound, and the stable compound is used for inhibiting the Akt pathway of the GRB2. And the key amino acid binding sites are Ile65, Gln157, Tyr160 and Phe182. Cell thermal transfer experiments (CETSA) show that PPVII can significantly enhance the thermal stability of GRB2 protein, surface plasmon resonance (SPR) determines the direct binding affinity KD = 58.5 [mu] M, functional research proves that PPVII inhibits an Akt signal channel through a GRB2 dependency mode, the polyphyllin VII is used as a GRB2 targeted inhibitor, and by specifically binding with an SH3 structural domain of GRB2 and inhibiting a downstream Akt signal channel, the polyphyllin VII can be used for inhibiting the Akt signal channel in the GRB2 targeted inhibitor. And a new strategy and a candidate compound are provided for intervention of related diseases.

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 safe conveying of oil and gas pipelines, in particular to a polypeptide type hydrate kinetic inhibitor screening method based on molecular simulation, which comprises the following steps: selecting target protein related to hydrate growth, and designing a polypeptide sequence; performing polypeptide pre-screening; evaluating the binding affinity and binding mode of the polypeptide and the target protein; performing MD simulation on the screened high-affinity polypeptide; verifying the binding affinity of the polypeptide and the target protein; and collecting all experiment and simulation data for statistical analysis, and optimizing the polypeptide sequence. The structure and function of the target protein are systematically analyzed by using a bioinformatics database and tools, it is ensured that the selected target plays an important role in hydrate formation, and meanwhile, a polypeptide sequence designed based on the target protein structure can effectively improve the binding capacity; and in the pre-screening and docking analysis process of the polypeptide, dynamic parameters are simulated and extracted by molecular dynamics, so that the interaction between the polypeptide and the target protein can be deeply understood.

A method for training a ligand information generation model performed by an electronic device includes obtaining sample receptor information and sample ligand information, a binding affinity between a ligand described by the sample ligand information and a receptor described by the sample receptor information being not less than a set affinity; denoising reference noise data based on the sample receptor information using a neural network model undergoing training to obtain predicted ligand information; determining a first loss for characterizing a difference between the sample ligand information and the predicted ligand information; and training the neural network model based on the first loss to obtain a ligand information generation model, the ligand information generation model being configured to generate reference ligand information based on reference receptor information.

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.

The invention relates to the field of biological medicine, and discloses a pTH long-acting polypeptide compound as well as preparation and application thereof. According to the polypeptide, at least one amino acid residue of the 13th, 26th and 27th amino acid residues of a pTH (1-34) parent peptide sequence is connected with octadecanedioic acid or eicosanoic acid and a derivative modification group of octadecanedioic acid or eicosanoic acid, and the polypeptide is covalently combined with a polypeptide skeleton through an AEA-AEA-gamma-Glu connecting unit. The binding capacity of the polypeptide and serum albumin is remarkably enhanced by utilizing a fatty acid side chain modification means, and meanwhile, the half-life period is prolonged. The pTH long-acting polypeptide compound disclosed by the invention has remarkable osteogenic activity promoting effect, can promote proliferation of MC3T3-E1 cells and generate osteogenic markers and calcium nodules under osteogenic induction conditions, and the binding capacity of the pTH long-acting polypeptide compound and serum albumin is improved by 2-6 times. The invention further provides a solid-phase synthesis method of the polypeptide compound and a pharmaceutical composition containing the polypeptide compound, the polypeptide compound can be used for treating osteoporosis and parathyroid hypofunction, and the compliance problem that an existing medicine needs to be injected every day is effectively solved.

This disclosure relates to an immunoglobulin single variable domain (ISVD)-containing modulator that allosterically binds to a three-dimensional (3D) epitope of a protein complex comprising at least one inhibitory immune receptor and at least one corresponding ligand. The modulator regulates cooperativity within such complexes, thereby affecting the binding affinity and downstream signaling pathways. Specifically, the allosteric modulator of this invention induces positive cooperativity in immunoinhibitory receptor-ligand complexes, thus suppressing immune responses in a spatiotemporally restricted manner. Accordingly, these allosteric modulators are useful as therapeutic agents for inflammatory diseases, such as autoimmune diseases, allergic diseases, or graft-versus-host disease (GVHD). Moreover, this disclosure pertains to methods for identifying, selecting, and producing said allosteric modulators.

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 present disclosure provides anti-B7-H3 antibody variants with enhanced antigen binding affinity. The present disclosure also provides methods for using the anti-B7-H3 antibody for treating a cancer or modulating the immune system in a subject.

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 disclosure provides Fc polypeptides wherein the Fc domain comprises at least one amino acid substitution that reduces binding affinity to an Fc receptor and / or effector function comprising one or more, two or more, three or more, four or more, or all five amino acid substitutions selected from L234A, L235A, G237A, K322A, and P329G, wherein the residues are numbered according to the EU index, preferably wherein the Fc polypeptide is an antibody. In some embodiments, the antibody is an anti-GIP antibody. In some embodiments, the antibody further comprises the three M252Y, S254T and T256E substitutions or the two M428L and N434S substitutions, which extend the half-life of the antibody.

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 invention relates to the field of biomedicine technology, and specifically discloses a dicyanoisophorone fluorescent probe for detecting brain β-amyloid protein, its preparation method and application. The fluorescent probe of the present invention is based on the dicyanoisophorone structure, and a probe with dual recognition sites is formed by introducing a carbamate group and an N,N-dimethylamino group. Compared with probes with a single recognition site, probes with dual recognition sites have a more sensitive fluorescent response to Aβ aggregates in vitro and show higher binding affinity and selectivity. The probe can effectively cross the blood-brain barrier and show high reactivity in the brains of Alzheimer's disease model mice. In addition, the probe can monitor the Aβ levels in the brains of Alzheimer's disease mice of different ages. It has great potential in the early diagnosis of neurodegenerative diseases.

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.

The invention relates to a computer-aided drug design technology, and provides a protein affinity prediction method and device, electronic equipment and a computer readable storage medium, the method comprises the following steps: obtaining a three-dimensional structure of a protein, the three-dimensional structure comprises a plurality of protein chains, and each protein chain comprises a plurality of amino acids; determining a feature vector of each amino acid according to a connection relationship between the amino acids, wherein the connection relationship comprises intra-chain connection between the amino acids belonging to the same protein chain and inter-chain connection between the amino acids belonging to different protein chains; and inputting the feature vectors of all amino acids into a pre-trained prediction model to obtain binding free energy of the protein, and calculating the affinity of the protein according to the binding free energy. According to the method, through intra-chain connection and inter-chain connection between the amino acids, the determined characteristics of the amino acids are more comprehensive, and accurate prediction of the protein-protein binding affinity is realized.

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.

A process for synthesizing and separating secretory IgA from a mixture of IgA monomer and IgA dimer is provided The process includes covalently binding affinity tagged or epitope tagged recombinant secretory component to the IgA dimer in the mixture and then binding the affinity tagged or an epitope tagged secretory IgA to immobilized moieties on the solid phase support resin to which the affinity tag or epitope tag binds and then eluting the affinity tagged or an epitope tagged secretory IgA with release buffer. A process for synthesizing and separating secretory IgM from a mixture of IgM and other plasma proteins is provided. A process is provided for inhibiting or preventing symptoms of necrotizing enterocolitis in a subject that includes the oral administration to the subject of a human polyclonal secretory IgA formed by the conjugation of human recombinant secretory component and pooled human plasma derived dimeric and polymeric.