Application progress of artificial intelligence in the screening and identification of drug targets / 中国药科大学学报

@#In recent years, artificial intelligence (AI) has developed rapidly, with improved computing power and algorithms, which has greatly facilitated the collection and processing of biological, chemical information and clinical data, injecting new vitality into the research and development of new drugs.In this review, we began with a brief overview of the development and the main algorithms of AI in drug discovery.Then we elaborated through several specific cases on the various scenarios of AI application, including target identification, protein structure prediction, hit generation and optimization etc.Finally, we focused on a recent example to discuss the high efficiency of "end-to-end" application of AI.

Research progress on the structure and function of the type IX secretion system of Porphyromonas gingivalis / 口腔疾病防治

@#The Porphyromonas gingivalis type IX secretion system (T9SS) is a recently discovered protein secretion system that is widely distributed in Bacillus cereus. The T9SS is structurally complex and powerful. More than 20 T9SS components have been verified, and more than 30 virulence factors can be secreted by Porphyromonas gingivalis alone, which contributes significant to the pathogenicity of Porphyromonas gingivalis. T9SS is a large protein complex spanning the inner cell membrane, periplasm, and outer cell membrane. Through the structural and functional connections among its components, it forms a sophisticated functional complex that includes power provision, energy transduction, inner and outer membrane translocation, outer membrane modification, and regulatory systems to recognize, translocate, shear, and modify cargo proteins and translocate bacterial intracellular cargo proteins to the cell surface. In recent years, with advancements in X-ray diffraction and in situ cryoelectron microscopy, the exploration of T9SS has evolved from the functional study of single components to the in situ structural study of multiprotein complexes. Still, the structural resolution of the protein still has shortcomings such as low resolution and an inability to capture dynamic functional structures. Future research directions should focus more on exploring how T9SS interacts and functions with cargo proteins. In this paper, we review the research progress on Porphyromonas gingivalis T9SS on X-ray diffraction and cryoelectron microscopy structure resolution in order to gain a deeper understanding of the transport mechanism of T9SS.

Biochemical properties of Scedosporium aurantiacum extracellular elastase-like protease / 生物工程学报

Extracellular elastase-like protease is one of the key virulence proteases of Scedosporium aurantiacum. To date, little is known about this enzyme in terms of genetic information, structure, properties and virulence mechanism due to the difficulties in purification caused by its low secretion amount, high specific activity, uncompleted genome sequencing and annotation. This work investigated the gene, structure and enzymatic properties of this enzyme. The S. aurantiacum elastase-like protease from the fungal culture supernatant was analyzed through tandem mass spectrometry (MS/MS) approach, illustrating its primary structure. Bioinformatics tools were employed to predict the conserved domain and tertiary structure, the enzymatic properties were also studied. It turned out that S. aurantiacum extracellular elastase-like protease demonstrated well hydrolysis towards elastin and bovine achilles tendon collagen, with Vmax of 18.14 μg/s and 17.57 μg/s respectively, better than fish scale gelatin, with the lowest hydrolysis effect on casein. Its activity towards elastin was lower than that of the elastase from porcine pancreas, with values of Kcat/Km of 3.541 (μg/s) and 4.091 (μg/s), respectively. It was an alkaline protease, with optimal pH 8.2 and temperature 37 oC. Zn2+ promoted the enzymatic activity while Ca2+, Mg2+, Na+, elastatinal and PMSF inhibited its activity. Its sequence was similar to Paecilomyces lilacinus secreted serine protease (PDB Entry: c3f7oB_) with multiple conserved fractions each containing more than 7 amino acids, thus suitable for design of PCR primer. This study increased our knowledge on S. aurantiacum extracellular elastase-like protease in terms of structure and enzymatic properties, and may facilitate later studies on protein expression and virulence mechanism.

Structure-guided engineering for improving the thermal stability of zearalenone hydrolase / 生物工程学报

Zearalenone is one of the most widely polluted Fusarium toxins in the world, seriously endangering livestock and human health. Zearalenone hydrolase (ZHD) derived from Clonostachys rosea can effectively degrade zearalenone. However, the high temperature environment in feed processing hampers the application of this enzyme. Structure-based rational design may provide guidance for engineering the thermal stability of enzymes. In this paper, we used the multiple structure alignment (MSTA) to screen the structural flexibility regions of ZHD. Subsequently, a candidate mutation library was constructed by sequence conservation scoring and conformational free energy calculation, from which 9 single point mutations based on residues 136 and 220 were obtained. The experiments showed that the thermal melting temperature (Tm) of the 9 mutants increased by 0.4-5.6 ℃. The S220R and S220W mutants showed the best thermal stability, the Tm of which increased by 5.6 ℃ and 4.0 ℃ compared to that of the wild type. Moreover, the thermal half-inactivation time at 45 ℃ were 15.4 times and 3.1 times longer, and the relative activities were 70.6% and 57.3% of the wild type. Molecular dynamics simulation analysis showed that the interaction force at and around the mutation site was enhanced, contributing to the improved thermal stability of ZHD. The probability of 220-K130 hydrogen bond of the mutants S220R and S220W increased by 37.1% and 19.3%, and the probability of K130-D223 salt bridge increased by 30.1% and 12.5%, respectively. This work demonstrated the feasibility of thermal stability engineering strategy where the structural and sequence alignment as well as free energy calculation of natural enzymes were integrated, and obtained ZHD variants with enhanced thermal stability, which may facilitate the industrial application of ZHD.

Sequence characteristics of Rhipicephalus microplus Enolase gene and prediction of structure and antigenic epitopes of its encoding protein / 中国血吸虫病防治杂志

Objective To analyze the sequence characteristics of Rhipicephalus microplus Enolase gene, and to predict the secondary and tertiary structure and antigenic epitopes of the Enolase protein. Methods Sixty-two engorged female R. microplus were sampled from a yellow cattle breeding farm in Zhijiang County, Huaihua City, Hunan Province in June 25, 2022. Genomic DNA was isolated from R. microplus, and the Enolase gene was amplified using PCR assay, followed by cloning, sequencing and expression of the amplification product. The sequence characteristics of the Enolase gene were analyzed using the software Clustal X, and the gene sequence was translated into amino acid sequences. The secondary and tertiary structures of the Enolase protein were deduced using the software PRABI, and the physicochemical properties of the Enolase protein were analyzed using the software PRABI. In addition, the B- and T-cell epitopes of the Enolase protein were predicted using the software ABCpred Prediction, Scratch, IEDB and NetCTL. Results The R. microplus Enolase gene sequence was 1 323 bp in size, and the contents of A, T, G and C bases were 24.5%, 22.5%, 27.0% and 26.0%,with 47.0% of A + T content and 53.0% of G + C content. The R. microplus Enolase gene encoded 434 amino acids, and the Enolase protein had a molecular weight of 47.12 kDa. The secondary structure of the Enolase protein contained 186 α-helixes (42.86%), 32 β-turns (7.37%), 144 random coils (33.18%) and 72 extended strands (16.59%). The Enolase protein was most probably present in cytoplasm (76.7%), followed by in mitochondrion (39.1%) and nucleus (21.7%), and the Enolase protein had no signal peptide or transmembrane domain. In addition, the Enolase protein had 14 B-cell dominant epitopes and 8 T-cell dominant epitopes. Conclusions The R. microplus Enolase gene sequence exhibits a GC preference, and its encoding Enolase protein is an acidic and hydrophilic protein, with α-helixes and random coils as its primary structure, and presenting B- and T-cell dominant epitopes, which is a potential target for development of vaccines against R. microplus.

Advances in heterologous expression, structural elucidation and molecular modification of pullulanase / 生物工程学报

Starch is composed of glucose units linked by α-1, 4-glucoside bond and α-1, 6-glucoside bond. It is the main component of foods and the primary raw material for starch processing industry. Pullulanase can effectively hydrolyze the α-1, 6-glucoside bond in starch molecules. Combined with other starch processing enzymes, it can effectively improve the starch utilization rate. Therefore, it has been widely used in the starch processing industry. This paper summarized the screening of pullulanase-producing strain and its encoding genes. In addition, the effects of expression elements and fermentation conditions on the production of pullulanase were summarized. Moreover, the progress in crystal structure elucidation and molecular modification of pullulanase was discussed. Lastly, future perspectives on pullulanase research were proposed.

An in vitro model mimicking the complement system to favor directed phagocytosis of unwanted cells

BACKGROUND: Opsonization, is the molecular mechanism by which target molecules promote interactions with phagocyte cell surface receptors to remove unwanted cells by induced phagocytosis. We designed an in vitro system to demonstrate that this procedure could be driven to eliminate adipocytes, using peptides mimicking regions of the complement protein C3b to promote opsonization and enhance phagocytosis. Two cell lines were used: (1) THP-1 monocytes differentiated to macrophages, expressing the C3b opsonin receptor CR1 in charge of the removal of unwanted coated complexes; (2) 3T3-L1 fibroblasts differentiated to adipocytes, expressing AQP7, to evaluate the potential of peptides to stimulate opsonization. (3) A co-culture of the two cell lines to demonstrate that phagocytosis could be driven to cell withdrawal with high efficiency and specificity. RESULTS: An array of peptides were designed and chemically synthesized p3691 and p3931 joined bound to the CR1 receptor activating phagocytosis (p < 0.033) while p3727 joined the AQP7 protein (p < 0.001) suggesting that opsonization of adipocytes could occur. In the co-culture system p3980 and p3981 increased lipid uptake to 91.2% and 89.0%, respectively, as an indicator of potential adipocyte phagocytosis. CONCLUSIONS: This in vitro model could help understand the receptor­ligand interaction in the withdrawal of unwanted macromolecules in vivo. The adipocyte-phagocytosis discussed may help to control obesity, since peptides of C3b stimulated the CR1 receptor, promoting opsonisation and phagocytosis of lipidcontaining structures, and recognition of AQP7 in the differentiated adipocytes, favored the phagocytic activity of macrophages, robustly supported by the co-culture strategy.

Deep learning: a new multifaceted tool assisting biomedical research and clinical diagnosis / 国际生物医学工程杂志

Artificial intelligence (AI) is one of the hottest research topics. The development of AI technology not only brings convenience to people's lives, but also integrates with other frontier fields to aid in data processing and result prediction. Deep learning is one of the emerging technologies that demonstrate outstanding performances. In this paper, the wide application of deep learning technology in many fields of biomedicine was summarized, common methods and models were briefly introduced including artificial neural network, deep neural network, convolutional neural network and recurrent neural network. Besides, the application of deep learning in biomedical image analysis, omics data processing and protein spatial structure prediction was summarized, and its limitations and development prospects in the above applications were briefly discussed.

Atractyloside targets the area of action of oncoprotein BORIS to inhibit cancer cell proliferation / 中国临床药理学与治疗学

AIM: To analyze the binding area of atractyloside targeting oncoprotein BORIS to inhibit cancer cell proliferation. METHODS: DNAMAN comparison sequences were used to find the conserved regions of BORIS. Conservative regions were elected and the structure were predicted using SWISS-MODEL. ChemBio3D Ultra was used for minimum structure quantification, and Autodocking for molecular docking. The BORIS of the corresponding segment were overexpressed for verification. RESULTS: BORIS-N end had relatively conserved regions and high-level structures in the biological evolution process. The N-terminal of human-derived BORIS was the main action area we speculated, especially the 70th to 97th amino acids, and the site that binded preferentially to atractyloside after molecular docking was the 96th position (Glutamine), and this area would inhibit cell proliferation. CONCLUSION: BORIS-N terminal and atractyloside have an action area, and this segment has an important effect on cell proliferation, which is of great significance for the future screening of targeted drugs.

Advances of structure, function, and catalytic mechanism of methyl-coenzyme M reductase / 生物工程学报

Methanogens are unique microorganisms for methane production and the main contributor of the biogenic methane in atmosphere. Methyl-coenzyme M reductase (Mcr) catalyzes the last step of methane production in methanogenesis and the first step of methane activation in anaerobic oxidation of methane. The genes encoding this enzyme are highly conserved and are widely used as a marker in the identification and phylogenetic study of archaea. There has been a longstanding interest in its unique cofactor F430 and the underpinning mechanisms of enzymatic cleavage of alkane C-H bond. The recent breakthroughs of high-resolution protein and catalytic-transition-state structures further advanced the structure-function study of Mcr. In particular, the recent discovery of methyl-coenzyme M reductase-like (Mcr-like) enzymes that activates the anaerobic degradation of non-methane alkanes has attracted much interest in the molecular mechanisms of C-H activation without oxygen. This review summarized the advances on function-structure-mechanism study of Mcr/Mcr-like enzymes. Additionally, future directions in anaerobic oxidation of alkanes and greenhouse-gas control using Mcr/Mcr-like enzymes were proposed.

PRIGSA2: Improved version of protein repeat identification by graph spectral analysis

Tandemly repeated structural motifs in proteins form highly stable structural folds and provide multiplebinding sites associated with diverse functional roles. The tertiary structure and function of these proteins aredetermined by the type and copy number of the repeating units. Each repeat type exhibits a unique pattern ofintra- and inter-repeat unit interactions that is well-captured by the topological features in the network representation of protein structures. Here we present an improved version of our graph based algorithm, PRIGSA,with structure-based validation and filtering steps incorporated for accurate detection of tandem structuralrepeats. The algorithm integrates available knowledge on repeat families with de novo prediction to detectrepeats in single monomer chains as well as in multimeric protein complexes. Three levels of performanceevaluation are presented: comparison with state-of-the-art algorithms on benchmark dataset of repeat and nonrepeat proteins, accuracy in the detection of members of 13 known repeat families reported in UniProt andexecution on the complete Protein Data Bank to show its ability to identify previously uncharacterizedproteins. A *3-fold increase in the coverage of the members of 13 known families and 3408 noveluncharacterized structural repeat proteins are identified on executing it on PDB. PRIGSA2 is available at http://bioinf.iiit.ac.in/PRIGSA2/.

Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility

Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal andoropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2aclade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were alsodetected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz.G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutationsreside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S2 domain,which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observedbetween these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations ofmiRNA binding and structure were also predicted for these mutations. More importantly, the possibleimplications of mutation D614G (in SD domain) and G1124V (in S2 subunit) on the structural stability of Sprotein have also been discussed. Results report for the first time a bird’s eye view on the accumulation ofmutations in SARS-CoV-2 genome in Eastern India.

Bioinformatic analysis of the structure and function of human TACSTD2 / 医学研究生学报

ObjectiveThe role of human tumor-related calcium signal transductor 2 (TACSTD2) in promoting tumorigenesis has been noticed recently. We predicted the molecular structure and biological function of TACSTD2 by bioinformatic methods, in order to provide reference for further study of TACSTD2.MethodsThe homo sapiens TACSTD2 mRNA and protein amino acid sequences were obtained from the National Center for Biotechnology Information (NCBI) database. The bioinformatic methods were used to analyze the open reading frame(ORF) of TACSTD2, physicochemical properties, signal peptide and protein localization, subcellular localization, and prediction of transmembrane structure and secondary structure, tertiary structure, potential protein modification sites, domains, protein modification sites proteins, protein interacting with TACSTD2, biological functions of TACSTD2, and expression of TACSTD2 in human normal tissues and certain tumor types.ResultsAccording to the mRNA sequence of TACSTD2, there are 12 ORFs, and the longest is ORF1, with a total of 972bp, encoding 323 amino acids. The hydrophilic amino acid of TACSTD2 is more than that of hydrophobic amino acid, indicating that TACSTD2 belongs to hydrophilic protein. TACSTD2 is a highly conserved alkaline secreted protein with a transmembrane region both inside and outside the cytoplasm. The presence of nuclear localization signal(NLS) in the amino acid sequence of TACSTD2 suggests that TACSTD2 can locate in cell nucleus. TACSTD2 mainly distribute in cytoplasmic membrane, extracellular, nucleus and cytoplasm. The secondary structure prediction results showed that the main structure of TACSTD2 was random coil, followed by a α helix. TACSTD2 has 15 serine modification sites, 17 threonine modification sites, and 8 tyrosine modification sites. The TACSTD2 has protein interactions with Claudin(CLDN) protein family; and participating in signaling pathway such as cell surface receptor, cell proliferation, negative regulation of epithelial cell migration, and so on. Comparing with normal human tissues, its mRNA expression is up-regulated in most tumor types such as cervical cancer, lung cancer, thyroid cancer, uterine cancer, liver cancer, colorectal cancer.ConclusionAccording to the analysis of the structure and function of TACSTD2, TACSTD2 is highly-expression in multiple malignancies. It can participate in the process of proliferation, migration and adhesion of malignant tumor cells through cell surface receptor signaling pathways. This study provide reference for the further research about the function of TACSTD2.

Bioinformatic analysis of the structure and function of human TACSTD2 / 医学研究生学报

ObjectiveThe role of human tumor-related calcium signal transductor 2 (TACSTD2) in promoting tumorigenesis has been noticed recently. We predicted the molecular structure and biological function of TACSTD2 by bioinformatic methods, in order to provide reference for further study of TACSTD2.MethodsThe homo sapiens TACSTD2 mRNA and protein amino acid sequences were obtained from the National Center for Biotechnology Information (NCBI) database. The bioinformatic methods were used to analyze the open reading frame(ORF) of TACSTD2, physicochemical properties, signal peptide and protein localization, subcellular localization, and prediction of transmembrane structure and secondary structure, tertiary structure, potential protein modification sites, domains, protein modification sites proteins, protein interacting with TACSTD2, biological functions of TACSTD2, and expression of TACSTD2 in human normal tissues and certain tumor types.ResultsAccording to the mRNA sequence of TACSTD2, there are 12 ORFs, and the longest is ORF1, with a total of 972bp, encoding 323 amino acids. The hydrophilic amino acid of TACSTD2 is more than that of hydrophobic amino acid, indicating that TACSTD2 belongs to hydrophilic protein. TACSTD2 is a highly conserved alkaline secreted protein with a transmembrane region both inside and outside the cytoplasm. The presence of nuclear localization signal(NLS) in the amino acid sequence of TACSTD2 suggests that TACSTD2 can locate in cell nucleus. TACSTD2 mainly distribute in cytoplasmic membrane, extracellular, nucleus and cytoplasm. The secondary structure prediction results showed that the main structure of TACSTD2 was random coil, followed by a α helix. TACSTD2 has 15 serine modification sites, 17 threonine modification sites, and 8 tyrosine modification sites. The TACSTD2 has protein interactions with Claudin(CLDN) protein family; and participating in signaling pathway such as cell surface receptor, cell proliferation, negative regulation of epithelial cell migration, and so on. Comparing with normal human tissues, its mRNA expression is up-regulated in most tumor types such as cervical cancer, lung cancer, thyroid cancer, uterine cancer, liver cancer, colorectal cancer.ConclusionAccording to the analysis of the structure and function of TACSTD2, TACSTD2 is highly-expression in multiple malignancies. It can participate in the process of proliferation, migration and adhesion of malignant tumor cells through cell surface receptor signaling pathways. This study provide reference for the further research about the function of TACSTD2.

Recent progress in 2-haloacid dehalogenases / 生物工程学报

2-Haloacid dehalogenases (EC 3.8.1.X) catalyze the hydrolytic dehalogenation of 2-haloacids, releasing halogen ions and producing corresponding 2-hydroxyacids. The enzymes not only degrade xenobiotic halogenated pollutants, but also show wide substrate profile and astonishing efficiency for enantiomer resolution, making them valuable in environmental protection and the green synthesis of optically pure chiral compounds. A variety of 2-haloacid dehalogenases have been biochemically characterized so far. Further studies have been made in protein crystal structures and catalytic mechanisms. Here, we review the recent progresses of 2-haloacid dehalogenases in their source, protein structures, reaction mechanisms, catalytic properties and application. We also suggest further research directions for 2-haloacid dehalogenase.

An in-gel digestion method of chymotrypsin to improve sequence coverage of membrane protein by mass spectrometry / 生物工程学报

In recent years, mass spectrometry has been widely used to study membrane protein structure and function. However, the application of mass spectrometry to study integral membrane protein is limited because there are many hydrophobic amino acids in the trans-membrane domain of integral membrane protein to cause low sequence coverage detected by LC-MS/MS. Therefore, we used vitamin K epoxide reductase (VKORC1), a human integral membrane protein, as a model to optimize the digestion conditions of chymotrypsin, and developed an in-gel digestion method of chymotrypsin to improve sequence coverage of membrane protein by mass spectrometry. By exploring the effects of calcium concentration, pH value and buffer system on the percentage of sequence coverage, number of total detected and types of unique peptide, and the size of unique peptide, sequence coverage and peptide diversity could be considered under condition of Tris-HCl buffer with 5-10 mmol/L calcium ion concentration and pH value 8.0-8.5. This method could make the sequence coverage of membrane protein to reach more than 80%. It could be widely used in the study of membrane protein structure and function, identification of interaction site between membrane proteins, and identification of binding site between membrane protein and small molecular drug.

Coronin,a novel potential target in tumor / 解剖学报

Coronin, a protein has a coronal-like pattern and locates below the cell membrane. Owing to its particular structure, coronin plays a key role in embryonic development and epithelial cell migration via its binding to microfilaments. Recently, proteins in coronin family were demonstrated that they could regulate the proliferation and migration of tumor cells through a series of molecular mechanisms, and there was a positive relationship between its abnormal expression and prognosis in the clinical patients. Therefore, its function and role in the progress of tumorigenesis is a hot topic in the current field of tumor research. In this paper, we made a comprehensive description of its molecular structural features, summarized its different roles in tumors, and predict its potential therapeutic prospects in the future.

Zika virus proteins at an atomic scale: how does structural biology help us to understand and develop vaccines and drugs against Zika virus infection?

In Brazil and in other tropical areas Zika virus infection was directly associated with clinical complications as microcephaly in newborn children whose mothers were infected during pregnancy and the Guillain-Barré syndrome in adults. Recently, research has been focused on developing new vaccines and drug candidates against Zika virus infection since none of those are available. In order to contribute to vaccine and drug development efforts, it becomes important the understanding of the molecular basis of the Zika virus recognition, infection and blockade. To this purpose, it is essential the structural determination of the Zika virus proteins. The genome sequencing of the Zika virus identified ten proteins, being three structural (protein E, protein C and protein prM) and seven non-structural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5). Together, these proteins are the main targets for drugs and antibody recognition. Here we examine new discoveries on high-resolution structural biology of Zika virus, observing the interactions and functions of its proteins identified via state-of-art structural methodologies as X-ray crystallography, nuclear magnetic resonance spectroscopy and cryogenic electronic microscopy. The aim of the present study is to contribute to the understanding of the structural basis of Zika virus infection at an atomic level and to point out similarities and differences to others flaviviruses.(AU)

Conjugation of NMR and SAXS for multidomain protein structure determination: from sample preparation to model refinement / Conjugación de NMR y SAXS para la determinación estructural de proteínas multidominio: de la preparación de muestras al refinamiento de modelo

Abstract Experimental information from small angle X-ray scattering (SAXS) is conjugated with nuclear magnetic resonance (NMR) spectroscopy data for the improvement of protein structure determination, particularly for flexible, multidomain or intrinsically disordered proteins. Individually, each of these techniques presents capabilities and limitations: NMR excels in local information, providing atomic resolution, but is limited by protein size, whereas SAXS yields a global envelope of the protein with lower resolution, but revealing domain positions. Different conjugation methodologies use the complementarity of both technique´s independent constraints to accomplish a comprehensive protein structure determination and dynamics understanding at a moderate computational expense.

Resumen Se conjuga información experimental proveniente de dispersión de rayos X a ángulos pequeños (SAXS) con la espectroscopía de resonancia magnética nuclear (NMR) para perfeccionar la determinación de la estructura protéica, en particular de proteínas flexibles, de multidominio o intrínsecamente desordenadas. Individualmente, cada una de estas técnicas presenta capacidades y limitaciones: NMR se destaca en la información local, proporcionando resolución atómica, pero está limitada por el tamaño de la proteína, mientras que SAXS produce una envoltura global de la proteína con una resolución menor pero revelando las posiciones de los dominios. Las diferentes metodologías de conjugación utilizan la complementariedad de las restricciones independientes de ambas técnicas para seguir estrategias adecuadas de acuerdo con la proteína, logrando una determinación integral de la estructura y una comprensión de las dinámicas del sistema proteico a un costo computacional moderado.

Bax protein structure and related research progress of eutectic structure / 国际生物医学工程杂志

Apoptosis involves multiple signaling pathways. The intrinsic signaling pathway is the mitochondrial apoptotic pathway, which is caused by a series of processes. First, the pro-apoptotic factors such as Bax are activated by signaling molecules and transfer to the mitochondrial outer membrane forming protein pores, thus the mitochondrial membrane permeability is affected, and then the downstream caspase-9 is activated and the apoptosis initiation is induced by releasing cytochrome C. In order to explore the apoptosis initiation activated by small molecules, the specific structural changes of Bax in apoptosis were studied. The results showed that there is a hydrophobic pocket structure near the C-terminal S184 of the Bax protein. This structure can be combined with certain small molecular substances specifically remove phosphorylation S184, and regulate Bax protein to promote apoptosis activity. At present, the nuclear magnetic structure of Bax protein has been obtained and the crystal structure has not been revealed. The eutectic structure formed by corresponding with other proteins in the Bcl-2 family has been resolved, which can be used to study the interactions between proteins and to understand the specific structural changes in the formation of heterologous dimers during apoptosis, site changes, etc. In this paper, the Bax protein structure resolved by nuclear magnetic structure was reviewed to learn the change of the sites in the induced apoptosis so as to promote the research on apoptosis initiation.