188 results about "Ligand molecule" patented technology

The present invention relates to the technical field of molecular interaction analysis, and specifically provides a method for analyzing intermolecular interactions. The method comprises the following steps: using a rare earth material with a ligand molecule modified on its surface as an upconversion material, contacting the upconversion material with a target molecule in a solution system, irradiating the solution system with excitation light that matches the rare earth material, and continuously changing the intensity of the excitation light actually received by the upconversion material as the target molecule continuously binds and dissociates with the ligand molecule of the upconversion material in a dynamic process, thereby changing the intensity of the emitted light. By recording the curve of the emission light intensity changing with time, the molecular interaction kinetic constants, such as the binding rate constant (K on ), dissociation rate constant (K off ) and affinity (K D ), etc., which solves the technical problems of low accuracy of existing BLI technology and high cost of SPR technology. Based on the above principles, the present invention has also developed a series of experimental consumables, kits, sensors and analytical devices for molecular interaction analysis.

The invention discloses a lysosome targeted chimera based on Sortilin and application thereof. The lysosome targeted chimera comprises a ligand molecule of a lysosome targeted receptor and a ligand molecule of a targeted protein to be degraded, wherein the ligand molecule and the ligand molecule are connected through a linker; the lysosome targeting receptor is Sortilin, and the ligand molecule of the lysosome targeting receptor is a polypeptide targeting the Sortilin; the protein to be degraded is membrane protein or extracellular protein. Furthermore, the polypeptide of the targeted Sortilin is connected with an enzyme response sequence and an integrin receptor targeting sequence. According to the invention, the Sortilin-combined ligand neurotensin is functionally coupled with the neutralizing antibody or polypeptide of overexpression protein in targeted tumor or inflammatory diseases, and the Sortilin-combined ligand neurotensin has obvious treatment gain in malignant solid tumor and psoriasis models. The discovery promotes the transformation potential of the lysosome participating in the biological agent, and provides a dual strategy for realizing accurate degradation through receptor recruitment and microenvironment induction.

The invention relates to the technical field of biology, in particular to a nucleic acid aptamer combined with TIDG6 protein, application and a screening method of the nucleic acid aptamer, and the nucleic acid aptamer has a nucleotide sequence as shown in SEQ ID NO.1; or a nucleotide sequence which has at least 30% homology with SEQ ID NO.1 and is combined with TIDG6 protein; the nucleic acid aptamer is an RNA sequence transcribed by a nucleotide sequence as shown in SEQ ID NO.1, or an RNA sequence transcribed by a nucleotide sequence as shown in SEQ ID NO.1. The nucleic acid aptamer is small in molecular weight, stable in chemical property, easy to store and mark, capable of being combined with TIDG6 protein with high affinity, very good in specificity, capable of being used in the aspects of detection, diagnosis, imaging, treatment and the like and wide in application prospect.

The invention belongs to the field of drug design, and particularly discloses a virtual screening method of a small-molecule inhibitor targeting YTHDF1 protein, which comprises the following steps: acquiring a YTHDF1 protein structure, and carrying out homologous modeling to generate various conformation proteins; small molecules combined with the YTHDF1 protein are obtained, bait molecules are generated, and ligand molecules are formed; a ligand molecule is in butt joint with a binding site on the YTHDF1, and the compound is characterized through PLEC fingerprints; the method comprises the following steps: constructing a specificity scoring function by using a machine learning algorithm, carrying out scoring screening on a compound to be screened and a compound butted with YTHDF1 molecules, carrying out affinity prediction, and screening out the small-molecule inhibitor targeting YTHDF1. According to the virtual screening method provided by the invention, the YTHDF1 targeting molecules with high affinity can be accurately screened on a large scale, candidate molecules are provided for research and development of medicines for treating YTHDF1 related diseases, and a foundation is laid for clinical tests and medicine optimization.

The invention discloses a two-dimensional bionic nanostructure assembled based on receptor-ligand acting force and a preparation method of the two-dimensional bionic nanostructure. The core characteristic of the two-dimensional bionic nanostructure is that the ultrafine particles modified by ligand molecules are anchored on the surface of a cell membrane fragment with a corresponding receptor expressed on the surface through a receptor-ligand effect, so that uniform compounding of the ultrafine particles and the cell membrane is realized; the bottlenecks of low compounding efficiency, functional site masking and the like caused by high surface curvature of small-size particles in the traditional cell membrane complete wrapping technology are broken through. According to the preparation method disclosed by the invention, the binding force between the cell membrane and the ultramicro particles is stronger, the off-target phenomenon of the ultramicro particles in the in-vivo circulation process can be avoided, the response release of the ultramicro particles under the competition effect in a lesion region expressed by a high-abundance receptor can be realized, and the preparation method has a good application prospect in the aspect of precise drug delivery. Meanwhile, the in-vivo circulation time of the ultrafine particles is prolonged by membrane loading, the biocompatibility of the ultrafine particles is improved, and the effectiveness and low toxicity of a drug delivery system are ensured.

The present disclosure relates to a structure-activity relationship analysis method and electronic device based on multidimensional interpretability, the method comprising: obtaining a series of ligand molecules; calculating target feature data of the series of ligand molecules, the target feature data including molecular descriptors, parent core structures, substituent groups and protein-ligand interactions; obtaining the real molecular activity data of each ligand molecule obtained based on experiments; using the target feature data of the ligand molecule as sample data, using the real molecular activity data as label data of the corresponding ligand molecule, and training the target machine learning model based on the sample data and label data; analyzing the target machine learning model based on the Shapley addition and interpretation algorithm to obtain the Shapley value of each target feature data; determining the influence of each target feature data on the molecular activity based on the Shapley value. The method aims to promote the intelligence and precision of structure-activity relationship analysis based on the interpretability of artificial intelligence models based on multidimensional feature representation and the Shapley addition and interpretation algorithm.

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 invention relates to the technical field of computational biology, and discloses a high-precision drug screening method and system based on hierarchical multi-modal representation learning, and the method comprises the steps: carrying out the feature extraction of an amino acid sequence of a target protein through a plurality of pre-trained protein language models; based on the three-dimensional structure of the target protein, multi-scale graph representation and ligand molecular graph representation of the protein are constructed; performing multi-modal feature learning on the multi-scale graph representation and the ligand molecular graph representation of the constructed protein by using a neural network based on message passing; and based on the multi-modal features, constructing a binding affinity prediction model for drug screening, and completing a drug screening task. A complex interaction relationship in a protein and ligand graph structure is effectively captured by using a multilayer graph neural network, and efficient coding of protein-ligand pair features is realized. The surface, the structure and the ligand embedding vector of the protein can be extracted, and the accuracy and the efficiency of protein-ligand interaction prediction are improved.

The invention discloses a construction method and device of a neural network model for target design drug molecules. According to the method, target pockets are characterized in three levels of atoms, residues and among the residues, so that the information of the target is more comprehensively considered; a molecular fragment obtained by a chemical structure inverse synthesis splitting algorithm is taken as a unit, the drug molecules are characterized and generated, and the generated molecules have higher drug forming potential; the model designed by the invention is composed of two neural network encoders and a gated self-attention decoder, the encoders are used for extracting features of a target and ligand molecules, the decoder realizes association of the two features and generates a molecular fragment probability, and the model can effectively design drug molecules for a specific target. Molecules designed by the model constructed by the invention have an average synthesis accessibility score of 0.769 and an average drug-likeness score of 0.607, which are higher than those of a baseline model PMDM.

The invention provides a rare earth complex as well as a preparation method and application thereof. The chemical general formula of the rare earth complex is (Ln < 1x > Ln < 2y > Ln < 31-x-y >) (A) m (B) n, the rare earth complex provided by the invention has a self-assembly behavior, spherical nanoparticles can be formed through molecular aggregation, under ultraviolet irradiation, internal ligand molecules are better protected, the photobleaching process of the rare earth complex under natural conditions is slowed down, and the rare earth complex has better stability and higher weather resistance in the natural environment.

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 method, the composition and the kit provided by the invention provide a signal amplification method for detecting target biomolecules, and the sensitivity of detecting by using target binding ligand molecules is remarkably improved. These methods include adding nucleic acid repeat cycles to, for example, a target binding molecule, thereby providing a plurality of landing pads for the labeled probe. These methods are well suited for multiplex detection, so that multiple targets can be sensitively detected in one detection. The methods and compositions can be applied to the fields of imaging, flow cytometry, mass spectrometers / CyTOF and the like, and provide additional tools for research and diagnosis purposes.

The application belongs to the technical field of food safety detection, and specifically discloses a method for detecting BaP in edible oil by using CTAB modified silver nanomaterial based on LLE-SERS, which comprises the following steps: preparing Ag nanoparticle sol, preparing CTAB functionalized Ag nanoparticle sol, SERS detection of BaP standard aqueous solution with different concentrations, fitting a standard curve, extracting BaP and performing SERS detection. The synthetic raw materials of the surface CTAB functionalized Ag nanoparticles used in the application are simple, and the coverage degree of the ligand molecules CTAB on the surface of the Ag nanoparticles can be controlled and adjusted. The CTAB as the surface ligand can directly capture and enrich BaP molecules. The detection method is high in stability, and can effectively avoid the problem that different batches of samples produce different effects in the Raman test.

The invention provides a DNTF eutectic ligand molecule prediction method based on multilayer information cross fusion, and the method comprises the steps: obtaining current to-be-detected DNTF crystal data, carrying out the preprocessing of the DNTF crystal data, obtaining the preprocessed DNTF crystal data, inputting the preprocessed DNTF crystal data into a trained DMSP network, and obtaining a prediction result of a DNTF crystal; wherein the trained DMSP network comprises a dynamic sparse projection layer, a multi-order interaction module, a structure perception module, a multi-level attention fusion module and a classifier; the DMSP network adopted by the invention can extract eutectic characteristic information which frequently appears and is clear in mode in crystal data through the explicit interaction layer in the multi-order interaction module, the potential characteristic information of eutectic is learned through the neural network of the implicit interaction layer, and finally, the information of the two view angles is fused, so that the eutectic characteristic information is obtained. And in combination with eutectic structure characteristics extracted from the structure sensing module, omnibearing capture of eutectic information is truly realized, so that the prediction accuracy is improved.

The application discloses a kind of based on active fragment's targeted ligand generation method, including fragment sequencing process: based on fragmentation method and sequencing method processing ligand molecule for training obtains fragment sequence;Model training process: ligand molecule fragment sequence and target protein amino acid sequence for training are input into targeted ligand molecule generation model, the molecular representation of ligand molecule fragment sequence is extracted by fragment sequence encoder, and the target representation of target protein amino acid sequence is extracted by target encoder, feature fusion is used after fragment sequence decoder output fragment sequence, and optimization model;Targeted ligand molecule generation process: target protein amino acid sequence is input into the model after training, the target representation is extracted by target encoder, and compound information is predicted by priori network and is input into fragment sequence decoder, and output fragment sequence, again based on molecular reconstruction method fragment sequence is recombined into targeted ligand molecule.

The invention provides a diketopyrrolopyrrole / cadmium quantum dot composite material as well as a preparation method and application thereof. The composite material comprises a composite material system formed by compounding diketopyrrolopyrrole derivative molecules and cadmium quantum dots. According to the invention, the rate and direction of fluorescence resonance energy transfer (FRET) between organic components and inorganic components in the composite material are simply and efficiently regulated and controlled by controlling the size of the quantum dots. The result of the embodiment shows that the composite material with the FRET rate of about 10 < 10 >-10 < 11 > s <-1 > can be obtained by adopting the method disclosed by the invention, and the energy transfer direction of FRET can be accurately regulated and controlled, so that energy transfer from ligand molecules to quantum dots or from quantum dots to ligand molecules is realized. The method is simple and convenient to operate and implement, and an inorganic-organic composite material system with broad-spectrum response can be constructed so as to realize efficient conversion and utilization of solar energy. In addition, the invention also provides a new thought for research and development in the fields of biological imaging, photoelectric devices and the like adopting a quantum dot-dye molecule composite material system.

This invention discloses a method for preparing cerium phytate complexes and their biological applications. A cerium ion aqueous solution is added to a phytic acid aqueous solution under stirring, and stirring continues until precipitation is complete. The mixture is then washed with ultrapure water until the washing solution is neutral, filtered, and dried to obtain a cerium phytate complex with a porous nanostructure. This invention utilizes a method for preparing cerium phytate complexes with the above-described structure and their biological applications, without using organic solvents, making the synthesis process safe and environmentally friendly. Phytic acid, as a ligand molecule constituting cerium phytate, has six phosphate groups, which can efficiently coordinate with cerium ions to form cerium phytate materials, exhibiting good thermal stability and ultraviolet absorption. The cerium phytate nanoparticles formed by the coordination of phytic acid and cerium ions carry a large amount of Ce. 3+ This is the basis for the antioxidant activity of cerium phytate. At the same time, the numerous pores inside the material effectively promote the adsorption of reactive oxygen free radicals, giving it highly efficient antioxidant properties, which can be applied to the treatment of various diseases related to reactive oxygen species.

The present invention discloses a polymer for target protein hydrolysis, a preparation method and a use thereof. The polymer of the present invention is combined with a target protein ligand and an E3 ligase ligand, and the polymer can solve the delivery problems existing in the existing delivery system in terms of water solubility, pharmacokinetic properties and cell membrane permeability. At the same time, the polymer prepared by the present invention can be assembled to form nanoparticles, which have natural targeting in vivo. In addition, the polymer of the present invention is a "multi-linker" type molecule, and the number and ratio of the side chain ligand molecules that bind to the target protein and the ligand molecules that recruit the E3 ligase can be flexibly adjusted, which is conducive to the construction of a combinatorial library for optimization, thereby obtaining the best protein degradation efficiency.

The application relates to the field of medicinal chemistry and provides a use of a diphenylacetonitrile compound and a protein-targeting hydrolytic chimeric compound. The application finds that a diphenylacetonitrile compound shown in formula (I) directly interacts with FEM1B, thereby serving as an inhibitor of a human E3 ubiquitin ligase substrate recognition receptor FEM1B. The application also provides a compound shown in formula (II), and the compound shown in formula (II) is a protein-targeting hydrolytic chimeric (PROTAC) drug, wherein Q2 is a target protein ligand molecule, Q1 is a FEM1B inhibitor, Q2 is combined with a target protein, thereby inducing E3 ligase FEM1B combined with Q1 to approach the target protein, leading to ubiquitination and degradation of the target protein. Experimental results show that the PROTAC drug shown in formula (II) provided by the application can specifically degrade a target protein in cells. Formula (I); formula (II).

The invention provides a DAPhen ligand, 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. Starting from the molecular structure design of the ligands, the novel DAPhen ligands are developed by designing the structures of the ligands, the ligands ensure the high distribution ratio of Eu, meanwhile, the introduction of the water-soluble ligands also ensures the efficient reverse extraction of Am, the lanthanum actinide separation factor SFEu / Am of the four DAPhen ligands is up to 320, and the separation effect is good. In addition, the ligand is good in water solubility and extraction kinetics, and balance can be achieved within 10 min. The invention provides a new thought for deeply understanding lanthanum actinide separation, and provides technical support for establishing an advanced spent nuclear fuel post-treatment system and efficiently utilizing minor actinide elements.

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 invention relates to a multi-metal zinc complex, a preparation method and application in polymer depolymerization. The multi-metal zinc complex forms a stable coordinate bond with an organic ligand molecular skeleton, shows excellent chemical stability and substrate adaptability, and can efficiently catalyze the depolymerization reaction of various polymers in a temperature range of 100-250 DEG C. In addition, the ligand framework has adjustability, polymer substrates with different compositions and structures can be optimized, and high-yield recovery of various types of monomers is realized. The catalytic system has wide applicability, can catalyze the bulk depolymerization of the polymer, and also can catalyze the depolymerization in the presence of a nucleophilic reagent. Through a multi-metal concerted catalysis mechanism, the dosage of the catalyst is remarkably reduced, various polymers with the number-average molecular weight in the range of 3.8-807.5 kg / mol can be depolymerized, the depolymerization reaction time is 0.5-24.0 h, side reactions are remarkably inhibited, and excellent industrial application prospects are shown.

The present invention provides a ribonucleic acid aptamer that binds to thrombin protein by improving screening conditions. The aptamer has a small molecular weight, stable chemical properties, and is easy to store and label. It can bind to the thrombin protein through spatial conformation matching, stacking of bases in the sequence, electrostatic interaction or hydrogen bonding between charged groups, etc., and has high binding affinity and good specificity. Therefore, the application of the aptamer in thrombin detection, imaging, regulation, etc. is also provided.

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.

This invention relates to the field of molecular docking technology, and discloses a method and system for screening female reproductive drugs in reproductive medicine. The method includes: constructing a female reproductive drug screening platform for target female users; defining a data parsing algorithm for the user interface; parsing reproductive examination data and reproductive needs into physiological parameters of the target user; mapping physiological states to relevant target proteins; retrieving molecular data of relevant target proteins; and matching ligand molecules of relevant target proteins. The method also includes: culturing target cells in vitro; adding ligand molecules to the in vitro cultured tissue; detecting cell activity, gene expression, and protein expression in the ligand test tissue; analyzing the enhancing effect of the ligand molecules on the ligand test tissue; calculating the gain coefficient of the enhancing effect; screening the optimal ligand molecules; and determining the female reproductive drugs for the target female users. This invention can improve the efficiency and accuracy of female reproductive drug screening in reproductive medicine.

The invention discloses a modification method of rare earth superfine nanowires, fluorescent ink and a preparation method and application of the fluorescent ink. The modification method comprises the steps that the rare earth superfine nanowires are dispersed in an organic solvent to obtain nanowire dispersion liquid, the nanowire dispersion liquid is modified through ligand molecules, and the modified rare earth superfine nanowires are obtained; by modifying the rare earth superfine nanowires, the luminescent property and dispersity of the rare earth superfine nanowires can be remarkably improved, the luminescent property of the fluorescent ink prepared by the invention is remarkably improved, different ligand molecules are selected to treat the rare earth superfine nanowires, the luminescent property of the fluorescent ink can be regulated and controlled, and the fluorescent ink has the advantages of high fluorescence intensity and strong adjustability.

The invention belongs to the technical field of food safety detection, and particularly discloses a method for detecting BaP in edible oil by using a CTAB modified silver nanomaterial based on LLE-SERS, and the method comprises the following steps: preparing Ag nanoparticle sol, preparing CTAB functionalized Ag nanoparticle sol, performing SERS detection on BaP standard substance aqueous solutions with different concentrations, fitting a standard curve, extracting BaP and performing SERS detection. The synthesis raw materials of the Ag nanoparticles with the CTAB functionalized surfaces are simple, and the coverage degree of ligand molecules CTAB on the surfaces of the Ag nanoparticles can be controlled and adjusted; cTAB (Cetyltrimethyl Ammonium Bromide) is used as a surface ligand to directly capture and enrich BaP molecules; the detection method disclosed by the invention is high in stability, and the problem that different batches of samples generate different effects in a Raman test is effectively avoided.

The application discloses a kind of bivalent ligand molecules for targeting BCL6 protein degradation and application thereof, it is related to the technical field of drug development;The structure general formula of the bivalent ligand molecules for targeting BCL6 protein degradation is as follows: M1-L-M2;Wherein, M1 and M2 are independent structure same or different BCL6 protein ligand;L is any chain or cyclic hydrocarbon fragment capable of forming covalent bond with BCL6 ligand.The application also provides the application of the bivalent ligand molecules in the preparation of anti-tumor and / or immune disease drugs.The bivalent ligand molecules can exert good anti-tumor activity on a variety of BCL6-dependent tumors by selectively inducing BCL6 protein degradation, and are also related to the occurrence of a variety of immune diseases, and can be used in related tumor and immune disease drugs.

According to embodiments of the present disclosure, a method, apparatus, device, storage medium, and program product for designing ligand molecules are provided. The method described herein comprises: editing a first 2D molecular structure to determine a second 2D molecular structure, the editing at least comprising: deleting a 2D structural fragment from the first 2D molecular structure, or adding a 2D structural fragment to the first 2D molecular structure; determining a set of candidate 3D molecular structures corresponding to the second 2D molecular structure based on a first 3D molecular structure corresponding to the first 2D molecular structure and the editing; determining a second 3D molecular structure corresponding to the second 2D molecular structure based on a binding capacity between the set of candidate 3D molecular structures and a target molecule; and determining a target structure of a ligand molecule for the target molecule based on the second 3D molecular structure. According to embodiments of the present disclosure, the generation of subsequent 3D molecular structures can be constrained based on the 3D molecular structure of the previous state, thereby improving the efficiency of designing ligand molecules.