103 results about "Protein stability" patented technology

The invention relates to the technical field of protein prediction, and discloses an efficient protein stability prediction method for selective state space modeling. According to the method, the BiMama core module and the CoGNN core module are adopted, and limitation of an existing method on calculation efficiency and multi-scale information processing is broken through in a mode of combining selective state space modeling and the collaborative graph neural network. According to the invention, a local sampling strategy based on a k-hop sub-graph is provided, and efficient calculation is realized by focusing a key environment around a mutation site; a bidirectional selective state space model is adopted to model a long-range dependency relationship with linear complexity, and the calculation bottleneck of a traditional Transform architecture is effectively overcome. The gating fusion module developed by the invention can adaptively integrate long and short range features, so that the model can flexibly adjust a feature combination strategy for different types of mutations, and the accuracy and efficiency of protein delta delta G prediction are improved.

Provided herein are technologies for framing and evaluating biological sequence-based analysis tasks in a unified, natural-language-based, text in and text out format. Among other things, methods and systems of the present disclosure provide machine-learning technologies for combining biological sequence data, representing, for example, DNA, RNA, and protein sequences, with natural language, conversational style prompts that set out particular analysis tasks to be performed on the biological sequence data. This approach, for example, allows complex analysis tasks, including, but not limited to, identification of various sequence modifications, genes, and regulatory elements in DNA sequences, and quantification of properties such as degradation propensity of RNA and protein stability, to be input to a machine learning model in a uniform text-based format and for output to be generated in a same, unified, text-based format.

The present disclosure provides drug responsive domains derived from human carbonic anhydrase 2 that can modulate protein stability for human interleukin 15 (IL15) payloads, as well as compositions and methods of use thereof.

The invention provides a protein mass spectrum data analysis method and system based on protein stability. The method comprises the following steps: determining scale constraint parameters of a sliding window during smoothing of protein mass spectrum data according to local noise variances at data points in the protein mass spectrum data; carrying out loss constraint on the edge of a protein stability characteristic peak in the protein mass spectrum data based on the scale constraint parameter in combination with a preset sliding window to obtain edge retention data of the protein stability characteristic peak; determining a fuzzy membership degree of each data point belonging to a protein stability characteristic peak according to a plurality of pre-identification peaks in the edge retention data and spatial distribution characteristics of each data point in the edge retention data; and performing baseline correction on the edge retention data based on Bayesian probability in combination with all fuzzy membership degrees, and further extracting peptide fragment signal peaks of the protein. According to the technical scheme provided by the invention, the effective peptide fragment signal peak in the protein mass spectrum data can be analyzed in a non-stationary background noise state.

A dual function protein is disclosed. The dual function protein may be prepared by linking a biologically active protein and an FGF mutant protein to an Fc region of an immunoglobulin. The dual function protein has improved pharmacological efficacy, in vivo duration and protein stability. The dual function protein exhibits improved pharmacological efficacy, in vivo duration and protein stability. A pharmaceutical composition containing the dual function protein as an active ingredient may be effectively used as a therapeutic agent for diabetes, obesity, dyslipidemia, metabolic syndrome, non-alcoholic fatty liver diseases, non-alcoholic steatohepatitis or cardiovascular diseases.

A coronavirus-targeting antibody nasal spray comprising: a coronavirus-targeting antibody or antigen-binding fragment, a buffer, a stabilizer, a surfactant, and a thickening agent, and optionally further comprising a preservative. The nasal spray can improve the physicochemical stability of the coronavirus-targeting antibody, and the nasal spray can maintain protein stability under conditions such as room temperature, long-term refrigeration, and repeated freeze-thawing, thereby improving the safety and effectiveness of clinical use.

The present disclosure relates to the use of a maltose dependent degron to control stability of a protein of interest fused thereto at the post-translational level. The present disclosure also relates to the use of a maltose dependent degron in combination with a maltose-responsive promoter to control gene expression at the transcriptional level and to control protein stability at the post-translational level. The present disclosure also relates to the use of a stabilization construct that couples expression of a cell-growth-affecting protein with the production of non-catabolic compounds. The present disclosure further relates to the use of a synthetic maltose-responsive promoter. The present disclosure further provides compositions and methods for using a maltose dependent degron, a maltose-responsive promoter, and a stabilization construct, either alone or in various combinations, for the production of non-catabolic compounds in genetically modified host cells.

The invention relates to application of a GSTP1 inhibitor in preparation of a medicine for treating chronic myelogenous leukemia, and belongs to the technical field of biomedicine. According to the application, it is found for the first time that interaction exists between CML core driving proteins BCR-ABL1 and GSTP1, GSTP1-mediated BCR-ABL1 protein glutathione modification can be effectively inhibited through targeted inhibition of the expression level of the GSTP1, the stability of the BCR-ABL1 protein is reduced, CML cell proliferation is inhibited, and CML cell apoptosis is promoted, so that the effect of treating the chronic myeloid leukemia is achieved. Therefore, the GSTP1 can be used as a treatment target, the GSTP1 inhibitor Ezatiostat is used for preparing the medicine for treating the chronic myelogenous leukemia, a theoretical basis and possibility are provided for developing a GSTP1 inhibitor and TKI combined medication scheme in the future, synergistic interaction is expected, and prognosis of a patient is further improved.

Disclosed herein are peptide hydrogel-based formulations. In some embodiments, the peptide hydrogel-based formulations encapsulate antibodies. In some embodiments, the peptide hydrogel-based formulations prevent formation of high molecular weight protein species.

The invention belongs to the technical field of action target screening and identification, and particularly relates to a method for screening and identifying a Nav channel protein binding agent based on ligand-induced protein stability change. The method comprises the following steps: firstly, carrying out mild lysis on cells of high-expression voltage-gated sodium ion channel protein (Nav channel protein) to obtain lysate containing active Nav channel protein, carrying out contrast incubation on the lysate, a compound to be detected and a solvent, carrying out restrictive enzymolysis by using protease in the presence of a surfactant, and carrying out freeze-drying to obtain the high-expression voltage-gated sodium ion channel protein (Nav channel protein). Representing the retention amount of the target protein and the internal reference protein, and evaluating the protective capability of the compound to be detected on degradation of the target protein to judge the affinity. The method has the advantages of high identification speed, economy and high efficiency, overcomes the problems that the existing Nav channel protein binding agent screening method is tedious, high in technical difficulty and depends on special large instruments, and can be used for screening action targets without specially constructing cells and purifying proteins by large instruments, so that the screening efficiency is effectively improved, and the screening cost is effectively reduced.

This invention discloses a mutant, gene, and recombinant bacteria of a highly thermostable single-chain sweet protein. The mutant is characterized by the following amino acid sequences shown in SEQ ID NO.1: isoleucine (I) at position 5 is mutated to glutamic acid (E), glutamic acid (E) at position 23 is mutated to alanine (A), isoleucine (I) at position 26 is mutated to arginine (R), cysteine ​​(C) at position 41 is mutated to alanine (A), tyrosine (Y) at position 65 is mutated to isoleucine (I), glycine (G) at position 83 is mutated to arginine (R), and asparagine (N) at position 90 is mutated to glutamic acid (E). Based on structural analysis and computationally assisted design for protein stability, this invention achieves site-directed mutagenesis of the single-chain sweet protein, resulting in a highly thermostable mutant. Compared to the original single-chain sweet protein, the thermostable mutant of this invention exhibits higher T... m It was heated by more than 20.4°C while maintaining its sweetness.

The invention relates to an application of a congenital non-ocular / microphthalmia related protein MAB21L1. The deletion and mutation of the MAB21L1 gene can cause non-ocular / microocular deformity. Specifically, the R51 site of the MAB21L1R51W mutant protein cannot form a salt bridge network with E49 and E115 sites, the protein stability is reduced, the MAB21L1R51W mutant protein is easily degraded by ubiquitin-proteasome, the expression of a key regulatory factor PAX6 for eye development cannot be promoted, and finally, the anophthalmia / microphthalmia is caused. An MAB21L1R51W human mutant cell strain and a zebra fish model are constructed based on a CRISPR / Cas9 technology, so that in-vivo and in-vitro combined research on an action mechanism of specific gene point mutation in eye development and diseases becomes possible, and a regulation mechanism of eye development diseases can be better understood; a new screening target is provided for antenatal molecular diagnosis of congenital azoopia / ommatidium diseases, and the method has positive practical significance.

Fusion proteins and methods for conditionally fine-tuning transposase protein stability and activity for clinical applications are provided herein

The application discloses a methionine adenosyltransferase mutant and application of the mutant in immobilized reaction, the mutant is obtained by mutating an amino acid sequence of wild-type Escherichia coli methionine adenosyltransferase, the mutant enhances the interaction force between subunits by introducing a disulfide bond at a specific position; and / or, the protein stability is enhanced by constructing a connecting peptide between adjacent subunits. The mutant provided in the application enhances the thermal stability and catalytic efficiency of the enzyme, reduces the optimum reaction pH value, reduces the generation of by-products and the precipitation of a reaction solution. The mutant enzyme can maintain high activity at a temperature of about 40 DEG C, and is particularly suitable for industrial production. In addition, the immobilized form of the mutant enzyme exhibits good stability and reusability in continuous use, significantly reduces production cost, simultaneously reduces environmental pollution, improves the yield of SAM, is more suitable for large-scale industrial production, and has more market competitiveness.

The present invention provides a recombinant sST2 protein, the amino acid sequence of the recombinant sST2 protein is shown in SEQ ID NO.3 or SEQ ID NO.5. Among them, the nucleotide sequence encoding the amino acid shown in SEQ ID NO.3 is shown in SEQ ID NO.4, and the nucleotide sequence encoding the amino acid shown in SEQ ID NO.5 is shown in SEQ ID NO.6. The recombinant sST2 protein prepared by the present invention has good performance, and the modified recombinant protein has a higher potency, which is better than the recombinant protein of the original sequence. The purity of the recombinant protein is ≥95%, and the activity is ≥95%; the protein stability is better, and it can be stored for one year at ‑20°C before reconstitution, and can be stored for more than 3 months at ‑20°C after reconstitution; the recombinant protein is close to the natural protein and has good interoperability with clinical samples. The recombinant proteins prepared by the present invention can be used for the preparation of calibrators and quality control products in the target detection kit, and can also be used for related experiments such as drug targeted analysis and drug development.

The application discloses a mutant and gene of single-chain sweet protein with high thermal stability, wherein the mutant is obtained by mutating isoleucine (I) at the 5th position, glutamic acid (E) at the 23rd position, isoleucine (I) at the 26th position, tyrosine (Y) at the 65th position, glycine (G) at the 83rd position and asparagine (N) at the 90th position in the amino acid sequence shown in SEQ ID NO. 1 to alanine (A), arginine (R), isoleucine (I), glutamic acid (E) and aspartic acid (D) respectively; the application is based on structural analysis and protein stability calculation aided design, and the single-chain sweet protein is subjected to site-directed mutagenesis, so that the mutant of single-chain sweet protein with high thermal stability is obtained; compared with the single-chain sweet protein, the mutant of single-chain sweet protein with high thermal stability has a T m increase of 18.4 DEG C or more and maintains sweetness.

The invention provides application of an expression inhibitor of KMT5A in preparation of a medicine for preventing or treating esophageal squamous carcinoma. In-vitro experiments prove that ICA can inhibit proliferation of esophageal squamous carcinoma cells in a concentration-dependent manner and remarkably promote cell apoptosis. The action mechanism of the ICA is closely related to the direct targeting KMT5A protein, and experiments show that the ICA can reduce the expression level of the KMT5A and influence the protein stability of the KMT5A. Clinical sample analysis further shows that KMT5A is highly expressed in esophageal cancer tissues, and ICA treatment in animal experiments significantly reduces the tumor volume. The invention provides a new targeted treatment strategy for esophageal squamous carcinoma, and has important clinical transformation value.

Embodiments of the present application provide a protein stability prediction method and device, computer equipment and a storage medium. The method comprises: obtaining a first to-be-tested sequence corresponding to an original protein and a second to-be-tested sequence corresponding to a mutant protein; determining a plurality of first target residue features from the first to-be-tested sequence according to the attention mechanism of the protein language model and extracting the global features thereof to obtain first virtual structure microenvironment features; similarly, obtaining second virtual structure microenvironment features corresponding to a plurality of second target residue features; determining a first difference based on the first virtual structure microenvironment features and the second virtual structure microenvironment features, and determining a second difference based on a first global sequence feature corresponding to the first to-be-tested sequence and a second global sequence feature corresponding to the second to-be-tested sequence; and predicting based on the first difference and the second difference to obtain a protein stability prediction result. In this way, the accuracy of predicting the stability of the protein can be improved.

The invention relates to the technical field of gene engineering and enzyme engineering, and discloses a sugarcane sucrose phosphate synthase truncation and application thereof, and the amino acid sequence of the truncation is as shown in SEQ ID NO.4. The sugarcane sucrose phosphate synthase truncation provided by the invention is obtained by cutting off 37th-42nd amino acids on the basis of a wild type sugarcane sucrose synthase (ScSPSB) gene from sugarcane cinnabar 42, and compared with the wild type ScSPSB gene, the sugarcane sucrose phosphate synthase truncation has higher catalytic activity and stability. According to the invention, a wild type ScSPSB gene is subjected to truncation transformation to obtain the sugarcane sucrose phosphate synthase truncation with higher catalytic activity and higher protein stability, so that a foundation is laid for studying transcription and expression mechanisms of sugarcane sucrose phosphate synthase and further discussing an accumulation mechanism of sucrose; and a theoretical and practical basis is provided for researching the biological function of the sucrose phosphate synthase and improving crop varieties by applying the sugarcane gene.

The invention relates to application of sericin to improvement of protein stability under various environmental pressures. Specifically, the sericin can promote denatured and inactivated protein renaturation / refolding so as to improve activity and stability, and can effectively stabilize various proteins including proteins, cell factors, enzymes, antibodies and the like under various environmental pressures, and the environmental pressures include high temperature, mechanical stress, acidic conditions, organic solvents, freeze-drying and multiple freeze-thawing. The sericin can also enhance the anticancer activity of specific glucose oxidase. The natural macromolecular sericin provided by the invention has the advantages of good biocompatibility, easiness in obtaining, low price and the like, and can be used as a wide protein stabilizer.

The invention provides a method for efficiently preparing high-purity NudCD3 protein in an in-vitro eukaryotic cell. The method comprises the following steps: synthesizing a target gene; carrying out enzyme digestion on the target gene and the pLEXmMBP vector, and connecting to obtain a recombinant vector; transforming the recombinant vector into competent cells, culturing, and extracting plasmids; transfecting an HEK 293F cell, culturing, and collecting the cell; resuspending the cells in a lysis buffer solution, carrying out ultrasonication and centrifugation, and taking a supernatant; and carrying out affinity chromatography column purification, Prescission protease digestion and molecular sieve purification to finally obtain the NudCD3 protein with the purity of more than 90%. The problems that in the prior art, NudCD3 protein is difficult to express in quantity and insufficient in purity are solved, high-purity protein is provided for structural biology research, drug screening and antibody preparation, and the method has the advantages of being easy to operate, high in yield, high in protein stability and the like.

The invention discloses an edible preservative capable of rapidly forming a film. The preservative is a chitosan-sodium alginate-acetic acid bacteria fermentation liquor-calcium chloride composite film (CSAC); the weight ratio of the cane sugar to the sodium alginate to the chitosan to the distilled water in the mixed solution is (4-6): (0.5-2): (1-3): 100, and the weight ratio of the mixed solution of the cane sugar to the sodium alginate to the chitosan to the acetic bacteria fermentation supernatant is 10: (1-3). The fresh-keeping application result of the mashed shrimps shows that after CSAC treatment, the change of color and luster of the mashed shrimps can be effectively reduced, the MDA content and TVB-N increase in tissues are delayed, the pH of the mashed shrimps is reduced, the water-retaining property is improved, and the comprehensive fresh-keeping effect is optimal. According to the method disclosed by the invention, acetic acid bacteria fermentation liquor is innovatively introduced into a chitosan-sodium alginate composite membrane system, and in-situ rapid membrane formation on the surface of the mashed shrimp is realized by utilizing calcium ion crosslinking. The CSAC film realizes comprehensive and efficient regulation and control of smooth color, protein stability, lipid oxidation, pH and water binding capacity of prawns through a synergistic effect of biological activity of a physical barrier and acetic acid bacteria metabolite.

The present disclosure relates to the use of a maltose dependent degron to control stability of a protein of interest fused thereto at the post-translational level. The present disclosure also relates to the use of a maltose dependent degron in combination with a maltose-responsive promoter to control gene expression at the transcriptional level and to control protein stability at the post-translational level. The present disclosure also relates to the use of a stabilization construct that couples expression of a cell-growth-affecting protein with the production of non-catabolic compounds. The present disclosure further relates to the use of a synthetic maltose-responsive promoter. The present disclosure further provides compositions and methods for using a maltose dependent degron, a maltose-responsive promoter, and a stabilization construct, either alone or in various combinations, for the production of non-catabolic compounds in genetically modified host cells.

The invention relates to the technical field of protease mutation, and discloses a bisabolol synthase mutant with high catalytic activity and application of the bisabolol synthase mutant. According to the method, alpha-bisabolol synthase derived from compositae herbaceous plant globe artichoke is taken as wild enzyme, mutants are virtually screened by applying a protein language model SaProt, a deep learning model Catapro and a protein stability prediction tool Dynaamt, and the effect of producing bisabolol is verified through experiments; according to the present invention, the mutants obtained by mutation of 11 specific amino acid sites such as D125N, F159Y, F159K, N346D, T372S, Y432F, N346S, D184E, N157E, E374A and T258S are obtained through the mutation of the above 11 specific amino acid sites; wherein through 96-hour shake flask fermentation and gas chromatography detection, the bisabolol yields of the obtained single-point mutation T258S and double-point mutation T258S / F159K are respectively increased by 72.6% and 90.2% compared with the wild type yield; the Kcat / Km value of the two-point mutation T258S / F159K is 4.57 times that of a wild type.

The application discloses a mutant of single-chain sweet protein with high thermal stability and a gene of the mutant, wherein the mutant is obtained by mutating isoleucine (I) at the 5th position, glutamic acid (E) at the 23rd position, isoleucine (I) at the 26th position, tyrosine (Y) at the 65th position, glycine (G) at the 83rd position and asparagine (N) at the 90th position in the amino acid sequence shown in SEQ ID NO. 1 to alanine (A), arginine (R) and aspartic acid (D) respectively. m The Tm of the mutant of single-chain sweet protein with high thermal stability is increased by more than 19.4 DEG C, and the sweetness is maintained.

The invention provides an application of an HIF-3alpha-3 gene or a protein coded by the HIF-3alpha-3 gene in preparation of a medicine for preventing and treating bladder cancer, and belongs to the technical field of biological medicines. The invention reveals that HIF-3alpha-3 in bladder cancer up-regulates PHD3 gene expression from a transcriptional regulation level, so that the hydroxylation level of HIF-1alpha in bladder cancer cells is increased, and the protein stability of HIF-1alpha is reduced for the first time. Meanwhile, overexpression of the HIF-3alpha-3 gene or the coded protein can effectively inhibit proliferation and in-vivo tumorigenicity of bladder cancer cells. Therefore, the invention provides the application of the HIF-3alpha-3 gene or the protein coded by the HIF-3alpha-3 gene or the PHD3 gene or the protein coded by the PHD3 gene in preparation of medicines for preventing and treating bladder cancer.

This invention belongs to the field of plant genetic engineering and relates to the application and method of reducing the expression of the Zm7649 gene in improving plant stress resistance. This invention utilizes an EMS mutant with premature termination of expression. Zm7649-ems Heterologous overexpression with Arabidopsis thaliana Zm7649-OE Verified Zm7649 The function of negatively regulating salt stress and high temperature stress was studied, and its preliminary analysis was performed. Zm00001d027649 The molecular mechanism regulating stress involves the interaction between Zm7649 and a maize catalase (Zm4848), with ubiquitination degrading Zm4848 and reducing its protein stability. This invention provides new genetic resources and theoretical basis for maize stress-resistance breeding or germplasm innovation.

Disclosed are a strain capable of expressing an exogenous protein, a recombinant human-derived collagen, a synthesis method, and the use. The present invention first provides the strain capable of expressing the exogenous protein, and the strain is proline-auxotrophic Escherichia coli and can efficiently express the exogenous protein. Using the strain as a host to express the recombinant human-derived collagen with supplementation of exogenous proline and hydroxyproline can achieve accurate regulation and control on the collagen hydroxylation rate by means of regulating the ratio of proline to hydroxyproline in a culture medium. By means of the synthesis method, a recombinant collagen of which the hydroxylation rate is approximate to that of natural human collagen can be obtained and has better cell adhesion and protein stability.

Provided herein are technologies for framing and evaluating biological sequence-based analysis tasks in a unified, natural-language-based, text in and text out format. Among other things, methods and systems of the present disclosure provide machine-learning technologies for combining biological sequence data, representing, for example, DNA, RNA, and protein sequences, with natural language, conversational style prompts that set out particular analysis tasks to be performed on the biological sequence data. This approach, for example, allows complex analysis tasks, including, but not limited to, identification of various sequence modifications, genes, and regulatory elements in DNA sequences, and quantification of properties such as degradation propensity of RNA and protein stability, to be input to a machine learning model in a uniform text-based format and for output to be generated in a same, unified, text-based format.

The present application relates to the construction method of the ophthalmic protein drug sustained-release preparation, the ophthalmic protein drug is contacted with the weakly interacting excipient of pharmaceutically acceptable, and the protein pre-holding complex is formed;The first hydration excipient and the second hydration excipient are sequentially added to the protein pre-holding complex, and the layered hydrated protein complex is formed;The layered hydrated protein complex is dispersed in the first continuous phase of the ionizable group-containing pharmaceutically high polymer, and the ion pairing release blocking layer is formed in the periphery by adjusting the ion environment, and the intermediate is obtained;The intermediate is dispersed in the second continuous phase of the ophthalmic pharmaceutically acceptable, and the ophthalmic protein drug sustained-release preparation is prepared.The ophthalmic protein drug is pre-held with the weakly interacting excipient, the differentiated occupation area and the layered hydration structure are constructed, the protein stability is improved;Through the stage ion regulation, the pharmaceutically high polymer forms the non-closed ion pairing release blocking layer, the protein release fine control is realized, the drug efficacy is prolonged and the curative effect is improved.