55 results about "Ligand molecule" patented technology

The invention relates to a UCNPs probe-based in-situ dynamic monitoring molecular interaction method, which comprises: S1, providing a UCNPs probe, the core layer of the UCNPs probe being a rare earth up-conversion nanocrystal, the shell layer of the UCNPs probe being an anti-quenching inert material, and the anti-quenching inert material coating the surface of the rare earth up-conversion nanocrystal; the surface of the anti-quenching inert material is modified with ligand molecules, and the ligand molecules are used for being specifically combined with target molecules in a to-be-detected sample; s2, mixing or contacting the UCNPs probe with a to-be-detected sample containing target molecules to construct a to-be-analyzed molecular interaction system; s3, irradiating the molecular interaction system by adopting near-infrared pulse laser, and collecting the change of the fluorescence lifetime tau of the UCNPs along with the time t and the change of the fluorescence intensity I along with the time t in real time to obtain a tau-t curve and an I-t curve; and S4, according to the tau-t curve and the I-t curve, realizing in-situ dynamic monitoring on the molecular interaction state. According to the method, a molecular binding / dissociation event is directly converted into a quantifiable and anti-interference optical signal, and the technical defect that in-situ dynamic monitoring of molecular interaction cannot be achieved in a traditional technology is overcome.

The embodiment of the invention discloses a protein-ligand interaction prediction method and a related device. Determining a prediction interaction pair formed by atoms of the protein and atoms of the ligand molecule according to the data of the protein and the data of the ligand molecule, establishing a loss function according to the node characteristics and the edge characteristics of the real interaction pair and the node characteristics and the edge characteristics of the prediction interaction pair, and adjusting model parameters according to the loss function, the target neural network model can be used for predicting the interaction between any protein and ligand molecules. Physical priori knowledge of protein-ligand interaction is fused in model training and prediction, so that the model can learn characteristics with more biological significance, and the predicted biological correlation is improved. According to the method, the advantages of deep learning are utilized, high-dimensional features are automatically extracted, complex pattern recognition is carried out, the complex relation in protein-ligand interaction is captured, and the stability and accuracy of protein-ligand interaction prediction are improved.

The invention discloses a ligand molecule generation method based on multi-modal information guidance, which fully captures high-precision interaction between a protein pocket and a ligand molecule, not only considers structural information of the ligand molecule, but also performs sufficient information guidance aiming at a protein target point molecule generation method. The generated molecules have diversity, and the requirements of subsequent biological docking experiment verification are met; on the other hand, the potential interaction relationship between the protein structure characteristics and the ligand molecules is utilized, different protein targets are fused in the diffusion process, and various modal information is balanced to guide the generation of the ligand molecules.

The application discloses a preparation method of a rare earth coordination type force-induced multi-fluorescent color variable gel, and comprises the following steps: dissolving a Schiff base ligand molecule, a monomer, an initiator and a crosslinking agent in deionized water, and stirring uniformly to obtain a stable solution, wherein the monomer is at least one of acrylamide, ethyl acrylate, methyl acrylate and methacrylic acid; adding a rare earth compound into the stable solution to obtain a prepolymer solution, and obtaining the rare earth coordination type force-induced multi-fluorescent color variable gel through free radical polymerization; the method has mild conditions, simple steps and is easy to realize. The application further discloses the force-induced multi-fluorescent color variable gel prepared through the preparation method; the types of the rare earth ions and the Schiff base ligand molecules are adjusted to obtain a multi-color fluorescent gel, and the visual fluorescent color change is realized under the action of external force. The force-induced multi-fluorescent color variable gel is combined with other functional materials to realize the integration of multiple functions, and can be applied to multiple fields such as optical devices and mechanical sensors.

The objective is to provide a novel method for improving the efficiency of osteogenic differentiation induction based on immobilized BMP-2. [Solution] A method for stimulating cells with ligand molecules, comprising a stimulation step of applying physical stimulation to the cells and / or ligand molecules, wherein the ligand molecule is bound to or interacts with a receptor protein expressed on the cells and is immobilized on a culture substrate and / or matrix molecule used for culturing the cells, the receptor protein mediates the transmission of extracellular signals to the cells based on its binding to the ligand molecule, and the extracellular signals are enhanced by the physical stimulation.

The invention discloses a molecular fragment library based on protein binding site properties and a construction method and application thereof, and belongs to the field of computer-aided drug design. The construction method comprises the following steps: acquiring three-dimensional structure data of a protein-ligand compound, and preprocessing to obtain standardized protein binding sites and ligand molecules; cutting the standardized ligand molecules by adopting an iterative molecular cutting algorithm to generate molecular fragments; identifying and quantifying an interaction between the molecular fragment and an amino acid residue in the normalized protein binding site; and associating the molecular fragments, the information of the amino acid residues interacting with the molecular fragments and the corresponding interaction modes, and constructing a molecular fragment library. The interaction mode of molecular fragments and specific amino acid residues is labeled, so that the targeting property of the fragment library is improved; and the candidate fragments with specific interaction potential can be quickly positioned, so that the drug design efficiency is improved.

The present invention addresses the problem of providing a novel method for increasing bone differentiation induction efficiency based on immobilized BMP-2.　Provided is a method for stimulating a cell with a ligand molecule, the method including a stimulation step for applying a physical stimulus to the cell and / or the ligand molecule. The ligand molecule binds to or interacts with a receptor protein expressed on the cell, and is immobilized on a culture substrate and / or a matrix molecule used for culturing the cell. The receptor protein mediates the transmission of an extracellular signal to the cell on the basis of binding to the ligand molecule, and the extracellular signal is enhanced by the physical stimulus.

This invention discloses an EGCG supramolecular compound with antioxidant, liver-protective, and fat-reducing effects, its preparation method, and composition. The supramolecular compound is formed by non-covalent bonding between epigallocatechin gallate (EGCG) and ligand molecules containing trimethylamine and carboxyl groups; the supramolecular compound has a co-amorphous structure; the ligand molecules containing trimethylamine and carboxyl groups are betaine, ergothioneine, or L-carnitine. This invention can solve the problems of low stability and bioavailability of EGCG. It can significantly improve the solubility of EGCG and its ligands, including betaine, L-carnitine, and ergothioneine, reduce the hygroscopicity of EGCG and its ligands, including betaine, L-carnitine, and ergothioneine, and enhance the stability and bioavailability of EGCG and its ligands, including betaine, L-carnitine, and ergothioneine.

The invention belongs to the technical field of fluorescence sensing, and particularly relates to a zinc-based coordination polymer based on a heterocyclic ligand and a preparation method and application thereof. The method comprises the following steps: dissolving 3, 7-dibromo-10H-phenothiazine, pyridine-4-boric acid and K2CO3 in a mixed solution of DMF (Dimethyl Formamide) and H2O, uniformly stirring, then adding tetrakis (triphenylphosphine) palladium, carrying out a heating reflux reaction under protective gas, removing a solvent after the reaction is finished, separating impurities, and purifying to obtain 3, 7-bis (4-pyridyl) phenothiazine; the preparation method comprises the following steps: preparing a heterocyclic ligand, dissolving the heterocyclic ligand and zinc nitrate hexahydrate in a mixed solution of DMF and H2O, uniformly stirring, heating to react, and washing and drying after the reaction is finished to obtain the zinc-based coordination polymer based on the heterocyclic ligand. According to the present invention, by using the butterfly conformation and electron donating effect of the ligand molecule 3, 7-bis (4-pyridyl) phenothiazine and the coordination binding capacity synergistic effect of pyridine, the ligand molecule 3, 7-bis (4-pyridyl) phenothiazine is coordinated with zinc ions to construct the novel material with excellent luminescence property;

The invention discloses a nucleic acid aptamer targeting RUNX1 protein and application thereof, and belongs to the technical field of biology, the nucleotide sequence of the nucleic acid aptamer is shown as RUNX1-5, and the nucleic acid aptamer is obtained through an in-vitro screening SELEX (systematic evolution of ligands by exponential enrichment) technology. The nucleic acid aptamer is small in molecular weight, is easy to chemically synthesize and functionally modify, has good physical and chemical stability, shows high affinity to the RUNX1 protein, has a dissociation constant lower than 30 nM, has good application prospects in the aspects of detection, separation and purification, marking and the like of the RUNX1 protein, and can also be used for preparing medicines for treating RUNX1 related diseases.

The application belongs to the technical field of separation and extraction, and particularly relates to a 8C-DAPhen ligand, a preparation method and application thereof. The method is developed from the design of a ligand molecular structure, and a novel cyclic DAPhen ligand is developed through specific structure design. The ligand has a separation factor (SF Eu / Am ) of more than 600 for lanthanide and actinide elements, and exhibits excellent separation performance. The application provides a new perspective for in-depth understanding of lanthanide and actinide separation mechanism, and provides technical support for establishing an advanced spent nuclear fuel reprocessing system and realizing efficient utilization of minor actinide elements.

The invention discloses an alpha-arylation reaction enantioselectivity prediction method based on machine learning. The alpha-arylation reaction enantioselectivity prediction method comprises the following steps: acquiring a reaction data set; calculating a physical and chemical descriptor based on a ligand molecular structure, and carrying out feature screening, standardization and dimension reduction processing on the descriptor to construct low-dimensional feature representation of the reaction; constructing and training a supervised machine learning regression model based on low-dimensional feature representation; and inputting a to-be-predicted ligand structure into the trained machine learning model to obtain a prediction result of the enantioselectivity of the alpha-arylation reaction, and applying the prediction result to virtual screening and optimization of candidate ligands. The method can effectively describe the influence of the ligand structure on the reaction enantioselectivity without depending on complex reaction mechanism assumption, realizes prediction of the enantioselectivity of the asymmetric catalytic reaction, and shows good generalization ability. According to the method, molecular structure characteristic engineering and machine learning modeling are combined, so that the accuracy of enantioselectivity prediction and the ligand screening efficiency are improved.

The application provides a method, device, equipment and computer readable storage medium for virtually screening coordination inhibitors, which comprises: obtaining a plurality of candidate ligand molecules containing at least one coordination warhead in a coordination warhead set; performing molecular docking on the plurality of candidate ligand molecules and target proteins respectively to obtain a plurality of molecular conformations after docking; screening a first set of molecular conformations according to the distance between the coordination warhead in the plurality of molecular conformations and the coordination center of the target protein; obtaining the first binding free energy of the first set of molecular conformations after docking with the target protein according to a first binding free energy calculation method, and screening a second set of molecular conformations; screening a third set of molecular conformations from the second set of molecular conformations, wherein the target molecular conformations in the third set of molecular conformations satisfy the first preset condition of the second binding free energy and / or the second preset condition of coordination energy; and determining the coordination inhibitor according to the third set of molecular conformations. The application can improve the screening efficiency and success probability of the coordination inhibitor.

The invention relates to preparation and application of a multi-substituent porous organic polymer catalyst. More specifically, the heterogeneous catalyst is composed of a metal active component and an organic polymer wherein the metal active component is one of metals Rh, Ru, Ir, Pd, Co or Cu; the multi-substituent porous organic polymer is a porous polymer generated by carrying out solvothermal copolymerization on a multi-substituent triaryl phosphine monomer. Substituent groups can influence dispersion force and electron transfer conditions in ligand molecules, and have remote regulation and control effects on metal site electron characteristics and steric hindrance, so that the catalytic performance of the catalyst is improved; the metal component and rich P atoms on the surface of the polymer carrier are coordinated to stably exist on the carrier, so that the heterogeneous catalyst shows excellent catalytic reaction activity and stability in the reaction, and the catalyst is easy to separate from reactants and products, and has great industrial application prospects.

The invention discloses an interaction perception comparison coding and multi-mode pocket feature driven molecule generation method and system. The method comprises the following steps: firstly, constructing a pre-training and fine-tuning data set; the method comprises the following steps: acquiring spatial interaction, structure and sequence features of protein pocket-ligand compound data, optimizing the sequence features through cross-modal contrast learning, and fusing the optimized sequence features with the structure features to obtain first multi-modal fusion features; constructing a molecule generation model, pre-training the model by using a pre-training data set, and then finely adjusting the model by using a second multi-modal fusion feature fused with the first multi-modal fusion feature and a corresponding ligand molecule sequence feature; for a specific target protein, the model can generate a molecule adapted to the specific target protein according to the multi-modal fusion feature of the pocket. The invention also discloses a system for realizing the method. The method and the system provided by the invention can effectively generate the candidate molecule which is highly matched with the binding site of the target protein, has high affinity and is excellent in synthesis accessibility.

The application provides a DEG-PTD ligand and a preparation method and application thereof, and a method for separating lanthanide elements and actinide elements from waste liquid, and belongs to the technical field of extraction separation. The application starts from the design of a ligand molecular structure, develops a new DEG-PTD ligand by designing the structure of the ligand, and ensures high distribution ratio for Eu, and meanwhile, the introduction of the water-soluble ligand also ensures efficient stripping for Am, 99% of 241Am loaded in the TODGA ligand organic phase can be stripped into the water phase, and the lanthanide-actinide separation factor SF of the DEG-PTD ligand is 1.5*10<4> Eu / Am The separation effect is good above 200. In addition, the ligand has good water solubility and extraction kinetics, and the water solubility is extremely good, and equilibrium can be reached in 5 min. The application provides a new idea for in-depth understanding of lanthanide-actinide separation, and provides important support for sustainable development of nuclear energy, scientific treatment and safe management of existing radioactive waste.

The invention relates to the technical field of biosensors, in particular to a transgenic corn CP4-EPSPS protein aptamer molecular beacon fluorescent biosensor. According to the invention, a systematic aptamer rational cutting and conformation adaptation strategy is constructed, the strategy obtains an initial aptamer through magnetic bead-SELEX screening, and the CP4-EPSPS protein aptamer is precisely cut and optimized by adopting the steps of loop region active core positioning, stem region structure optimization and base binding domain identification, so that the binding performance and the structural stability are remarkably improved. Subsequently, on the basis of stable conformational characteristics, a complementary chain competition sensing mechanism is designed, and a transgenic corn CP4-EPSPS protein aptamer molecular beacon fluorescent biosensor is successfully constructed, so that amplification-free high-sensitivity rapid detection of CP4-EPSPS protein is realized, and a solution is provided for supervision of transgenic crops.

This invention provides a liver-targeting glycoligand molecule modified with dual-antenna GalNAc and its drug delivery system. This liver-targeting glycoligand molecule and its drug delivery system, through ASGPR recognition, can maximize the concentration of therapeutic drugs in liver tumor parenchymal cells, thereby improving the targeting of drug distribution, increasing the therapeutic index, reducing systemic toxicity, and improving patient survival time and quality of life. The liver-targeting glycoligand molecule of this invention is synthesized using an enzymatic synthesis method, which involves fewer synthesis steps, mild enzymatic reaction conditions, high regioselectivity, high reaction efficiency, is environmentally friendly, and has low production costs, making it highly promising for industrialization.

The application relates to a virtual screening method, device and electronic equipment. The method comprises the following steps: performing molecular docking on ligand molecules in a molecule library and target proteins to obtain at least one molecular conformation after the ligand molecules contact the target proteins; determining a first binding free energy of the molecular conformation after the ligand molecules contact the target proteins by using a preset scoring function, and screening a molecular conformation whose first binding free energy meets a first preset condition; and determining a second binding free energy of the molecular conformation whose first binding free energy meets the first preset condition after the ligand molecules contact the target proteins based on a semi-empirical molecular orbital method, and screening a molecular conformation whose second binding free energy meets a second preset condition. The scheme provided by the application can quickly predict the binding free energy of the molecular conformation, improve the accuracy of the prediction result, and thus improve the success rate of screening active compounds.

This invention discloses a bivalent ligand molecule targeting EGFR and its applications, belonging to the field of drug development technology. Its general structural formula is: [Formula omitted for brevity], where L is a linking group, and M1 and M2 are EGFR protein ligands. This invention forms a bivalent EGFR ligand molecule by covalently linking two EGFR ligands through a linking group. This bivalent ligand molecule can induce additional protein-protein interactions between EGFR monomers, which greatly enhances the binding strength and stability of the drug to EGFR, thereby overcoming the drug resistance problem of traditional EGFR inhibitors and providing a new treatment strategy for cancer patients carrying EGFR mutations and other patients with other diseases.

The application discloses a DNA aptamer binding to LOX-1 protein and application thereof. Specifically, the application provides a DNA aptamer binding to LOX-1 protein, wherein a core sequence of the DNA aptamer binding to the LOX-1 protein comprises a sequence as shown in SEQ ID NO: 5. The aptamer has small molecular weight, stable chemical property, is easy to preserve and label, can be combined with the LOX-1 protein through space conformation matching, accumulation of bases in a sequence, electrostatic interaction between charged groups or hydrogen bond interaction, and the like, has high affinity and good specificity.

This invention relates to the field of molecular generation technology, and discloses a method for constructing a molecular generation model and a molecular generation method. The method includes: acquiring a multimodal sample dataset, which comprises several protein sample groups. Each protein sample group includes pocket structure information of the target protein, ligand molecule information binding to the target protein pocket, textual description information of the target protein pocket, and molecular fragment constraint information; training a language learning model based on the multimodal sample dataset to obtain a molecular generation model. This invention enables the model to fully integrate multi-dimensional conditional information within a unified training framework, effectively improving the model's control over the molecular generation process and the accuracy of structure prediction. The generated molecules can efficiently bind to the target protein pocket while meeting semantic requirements and structural constraints, effectively adapting to the complex and multi-constrained design requirements in real-world drug development.

This invention discloses a molecular generation method based on a variable flow model using protein structure, comprising the following steps: Step 1: Obtain the pdb format file of the protein receptor for which ligand molecules need to be generated; Step 2: Assuming the protein receptor for which ligand molecules need to be generated comprises p atoms, extract the atom type features and atom spatial position features of the protein receptor; the atom type features are feature vectors of size p×1, and the atom spatial position features are feature vectors of size p×3; the atom spatial position includes: distance, bond angle, and dihedral angle; Step 3: Input the extracted atom type features and atom spatial position features of the protein receptor into a pre-trained molecular generation model GraphSF to generate several atoms; Step 4: Add bonds according to the interatomic distances, and finally output the corresponding ligand molecule in SDF format.

This invention belongs to the field of analytical chemistry and relates to the preparation and sensing applications of highly efficient electrochemiluminescent gold nanoclusters protected by co-reactive ligands. This invention synthesizes a class of gold nanoclusters protected by co-reactive ligands, whose ligand molecular backbone includes terminal thiol groups as anchoring groups and a tertiary amine structure. Using co-reactive ligands as stabilizers, a one-pot method is employed to synthesize highly efficient electrochemiluminescent gold nanoclusters. This method not only stabilizes the gold nanoclusters, preventing them from agglomerating and losing their optical properties, but also utilizes the tertiary amine structure to function as a co-reactant. This allows the synthesized gold nanoclusters to generate highly efficient anodic near-infrared electrochemiluminescence without the participation of exogenous co-reactants, providing an opportunity for the preparation of highly sensitive and convenient sensors, high-brightness organic light-emitting diodes, and deep tissue imaging research. Simultaneously, it enables highly sensitive, highly specific, and convenient detection of carboxylesterases, providing a new method for the early clinical diagnosis of hepatocellular carcinoma.

The invention provides a nano-complex for inducing tumor cell pan-apoptosis. The nano-complex is formed by coordination of zinc ions, a first ligand and a second ligand, the first ligand is 2-methylimidazole; the second ligand is a cis-platinum prodrug ligand, and the structure of the second ligand is shown in the specification. An imidazole nitrogen atom in a cisplatin prodrug ligand molecule, a cisplatin prodrug ligand and 2-methylimidazole are competitively coordinated with zinc ions together, so that a cisplatin prodrug is coordinated into a ZIF-8 nano-particle, and the hybrid nano-particle which is coordinated by diaminoimidazole and has a ZIF-8 crystal structure is formed. The invention also provides a preparation method of the nano-composite and application of the nano-composite in preparation of antitumor drugs. The ZIF-8 nanoparticles obtained by the preparation method disclosed by the invention show positive electricity and can also be used as a gene delivery carrier, and the system can effectively activate the pan apoptosis of drug-resistant cells and has potential application value in the aspect of drug-resistant tumor treatment.

The present disclosure is based on the surprising and unexpected discovery that a ligand molecule with certain characteristics is able to bind to two protein molecules simultaneously and recruit them to form a transient or stable protein-protein interaction complex. The protein-protein interaction and other cross-domain interactions gained in this process contribute additional stabilization energy to the complex beyond the combination of the binary binding energies, and therefore, largely increase the binding potency of the ligand. Accordingly, the present disclosure provides a Protein-Protein Interaction Inducing Technology (PPIIT), which includes a method to design and identify the tripartite or bifunctional compounds and use such compounds to induce protein-protein interactions in various contexts. The present disclosure also provides a composition for the purpose of inducing protein-protein interactions.

The application belongs to the technical field of extraction separation, and particularly relates to an OE-DAPhen ligand, a preparation method and application thereof. The application develops a novel DAPhen ligand through specific structure design from the design of a ligand molecular structure. The separation factor (SF) of the OE-DAPhen ligand for lanthanide and actinide elements is more than 400, and the OE-DAPhen ligand exhibits excellent separation performance. The application provides a new perspective for in-depth understanding of lanthanide and actinide separation mechanism, and provides technical support for establishing an advanced spent nuclear fuel reprocessing system and realizing efficient utilization of minor actinide elements. Eu / Am ).

A method, kit, sensor and device for analyzing intermolecular interaction. In the method for analyzing intermolecular interaction, a rare-earth material of which the surface is modified with ligand molecules is used as an up-conversion material; the up-conversion material comes into contact with target molecules in a solution system; excitation light matching the rare-earth material is used to irradiate the solution system; in a dynamic process of continuous association / dissociation between the target molecules and the ligand molecules on the up-conversion material, the intensity of excitation light actually received by the up-conversion material continuously changes, such that the intensity of emitted light changes; and by recoding a curve of the intensity of the emitted light changing with time, kinetic constants of molecular interaction, such as an association rate constant (Kon), a dissociation rate constant (Koff), and affinity (KD), are calculated. In this way, existing technical problems of low accuracy of BLI technology and high costs of SPR technology.

The invention relates to the technical field of drugs and the technical field of artificial intelligence, in particular to a protein-ligand binding affinity prediction method and system for drug research and development, and the method comprises the steps: obtaining a protein-ligand pair, and extracting structure-perceived protein characterization, functional characterization and ligand molecular characterization; wherein the protein characterization is determined by an amino acid sequence and structural information of the protein, and the function characterization is determined by the protein with function annotation information; performing token dimension alignment on the protein characterization and the functional characterization based on a multi-layer perceptron (MLP), performing multi-modal fusion on the aligned protein characterization and functional characterization, and obtaining a fused embedded representation by combining a token-by-token adaptive weight alpha; and splicing the fused embedded representation and ligand molecular representation to obtain a comprehensive feature vector for predicting binding affinity. Through deep interaction and fusion of multi-source information such as sequence, structure and function annotation, the accuracy of protein-ligand affinity prediction is improved.