Proteins-Structure Function and Bioinformatics最新文献_第8页

Integrative Modeling in the Age of Machine Learning: A Summary of HADDOCK Strategies in CAPRI Rounds 47-55.

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2024-12-30 DOI: 10.1002/prot.26789

Victor Reys, Marco Giulini, Vlad Cojocaru, Anna Engel, Xiaotong Xu, Jorge Roel-Touris, Cunliang Geng, Francesco Ambrosetti, Brian Jiménez-García, Zuzana Jandova, Panagiotis I Koukos, Charlotte van Noort, João M C Teixeira, Siri C van Keulen, Manon Réau, Rodrigo V Honorato, Alexandre M J J Bonvin

{"title":"Integrative Modeling in the Age of Machine Learning: A Summary of HADDOCK Strategies in CAPRI Rounds 47-55.","authors":"Victor Reys, Marco Giulini, Vlad Cojocaru, Anna Engel, Xiaotong Xu, Jorge Roel-Touris, Cunliang Geng, Francesco Ambrosetti, Brian Jiménez-García, Zuzana Jandova, Panagiotis I Koukos, Charlotte van Noort, João M C Teixeira, Siri C van Keulen, Manon Réau, Rodrigo V Honorato, Alexandre M J J Bonvin","doi":"10.1002/prot.26789","DOIUrl":"https://doi.org/10.1002/prot.26789","url":null,"abstract":"The HADDOCK team participated in CAPRI rounds 47-55 as server, manual predictor, and scorers. Throughout these CAPRI rounds, we used a plethora of computational strategies to predict the structure of protein complexes. Of the 10 targets comprising 24 interfaces, we achieved acceptable or better models for 3 targets in the human category and 1 in the server category. Our performance in the scoring challenge was slightly better, with our simple scoring protocol being the only one capable of identifying an acceptable model for Target 234. This result highlights the robustness of the simple, fully physics-based HADDOCK scoring function, especially when applied to highly flexible antibody-antigen complexes. Inspired by the significant advances in machine learning for structural biology and the dramatic improvement in our success rates after the public release of Alphafold2, we identify the integration of classical approaches like HADDOCK with AI-driven structure prediction methods as a key strategy for improving the accuracy of model generation and scoring.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2024-12-26 DOI: 10.1002/prot.26785

Matthias Fellner, George Randall, Ianah R C G Bitac, Annmaree K Warrender, Ashish Sethi, Raz Jelinek, Itamar Kass

{"title":"Similar but Distinct-Biochemical Characterization of the Staphylococcus aureus Serine Hydrolases FphH and FphI.","authors":"Matthias Fellner, George Randall, Ianah R C G Bitac, Annmaree K Warrender, Ashish Sethi, Raz Jelinek, Itamar Kass","doi":"10.1002/prot.26785","DOIUrl":"https://doi.org/10.1002/prot.26785","url":null,"abstract":"Staphylococcus aureus is a major cause of infections like bacteremia, pneumonia, and endocarditis. These infections are often linked to the ability of S. aureus to form biofilms. Several S. aureus serine hydrolases have previously been identified to be active during biofilm-forming conditions. Here, we present the biochemical characterization of two of these enzymes-fluorophosphonate binding hydrolase H and I (FphH, FphI). Cryogenic and room-temperature X-ray crystallography, enzymatic substrate profiling, small-angle X-ray scattering analysis, and molecular dynamics simulations provide new insights into similarities and differences between these two hydrolase_4 domain family members. We discover that these enzymes share an overall fold, including a flexible lid or cap region above the active site, which can be seen to be mobile in solution. Differences in the active site pocket and lid residues differentiate them and explain speed differences in their carboxyesterase substrate profile toward small unbranched carbon chain ester molecules. The first analysis of FphI is also compared to our previous knowledge of FphH and its association to stress conditions. These results enable the future precise targeting of Fph serine hydrolase family members with a long-term goal to significantly improve the health and wellbeing of individuals and populations worldwide.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142900932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cryo-EM Structure of Human Hyaluronidase PH-20. 人透明质酸酶PH-20的低温电镜结构。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2024-12-25 DOI: 10.1002/prot.26788

Seong-Bin Im, Hyung Nam Song, Tae-Kyeong Jeong, Nayun Kim, Kyuwan Kim, Soon-Jae Park, Byung-Ha Oh

引用次数: 0

Exploring Compactness and Dynamics of Apomyoglobin. 无肌红蛋白的致密性和动力学研究。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2024-12-23 DOI: 10.1002/prot.26786

Anna V Glyakina, Mariya Y Suvorina, Nikita V Dovidchenko, Natalya S Katina, Alexey K Surin, Oxana V Galzitskaya

{"title":"Exploring Compactness and Dynamics of Apomyoglobin.","authors":"Anna V Glyakina, Mariya Y Suvorina, Nikita V Dovidchenko, Natalya S Katina, Alexey K Surin, Oxana V Galzitskaya","doi":"10.1002/prot.26786","DOIUrl":"https://doi.org/10.1002/prot.26786","url":null,"abstract":"Hydrogen-deuterium exchange mass spectrometry (HDX-MS) approach has become a valuable analytical complement to traditional methods. HDX-MS allows the identification of dynamic surfaces in proteins. We have shown that the introduction of various mutations into the amino acid sequence of whale apomyoglobin (apoMb) leads to a change in the number of exchangeable hydrogen atoms, which is associated with a change in its compactness in the native-like condition. Thus, amino acid substitutions V10A, A15S, P120G, and M131A result in an increase in the number of exchangeable hydrogen atoms at the native-like condition, while the mutant form A144S leads to a decrease in the number of exchangeable hydrogen atoms. This may be due to a decrease and increase in the compactness of apoMb structure compared to the wild-type apoMb, respectively. The L9F and L9E mutations did not affect the compactness of the molecule compared to the wild type. We have demonstrated that V10A and M131A substitutions lead to the maximum and large increase correspondently in the average number of exchangeable hydrogen atoms for deuterium, since these substitutions lead to the loss of contacts between important parts of myoglobin structure: helices A, G, and H, which are structured at the early stage of folding.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SUPERMAGO: Protein Function Prediction Based on Transformer Embeddings. 基于变压器嵌入的蛋白质功能预测。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2024-12-22 DOI: 10.1002/prot.26782

Gabriel Bianchin de Oliveira, Helio Pedrini, Zanoni Dias

{"title":"SUPERMAGO: Protein Function Prediction Based on Transformer Embeddings.","authors":"Gabriel Bianchin de Oliveira, Helio Pedrini, Zanoni Dias","doi":"10.1002/prot.26782","DOIUrl":"https://doi.org/10.1002/prot.26782","url":null,"abstract":"Recent technological advancements have enabled the experimental determination of amino acid sequences for numerous proteins. However, analyzing protein functions, which is essential for understanding their roles within cells, remains a challenging task due to the associated costs and time constraints. To address this challenge, various computational approaches have been proposed to aid in the categorization of protein functions, mainly utilizing amino acid sequences. In this study, we introduce SUPERMAGO, a method that leverages amino acid sequences to predict protein functions. Our approach employs Transformer architectures, pre-trained on protein data, to extract features from the sequences. We use multilayer perceptrons for classification and a stacking neural network to aggregate the predictions, which significantly enhances the performance of our method. We also present SUPERMAGO+, an ensemble of SUPERMAGO and DIAMOND, based on neural networks that assign different weights to each term, offering a novel weighting mechanism compared with existing methods in the literature. Additionally, we introduce SUPERMAGO+Web, a web server-compatible version of SUPERMAGO+ designed to operate with reduced computational resources. Both SUPERMAGO and SUPERMAGO+ consistently outperformed state-of-the-art approaches in our evaluations, establishing them as leading methods for this task when considering only amino acid sequence information.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction to "Allosteric Modulation of Fluorescence Revealed by Hydrogen Bond Dynamics in a Genetically Encoded Maltose Biosensor". 修正“基因编码麦芽糖生物传感器中氢键动力学揭示的荧光变构调制”。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2024-12-20 DOI: 10.1002/prot.26787

引用次数: 0

Distribution of Polyphosphate Kinase 2 Genes in Bacteria Underscores a Dynamic Evolutionary History. 多磷酸激酶 2 基因在细菌中的分布证明了动态进化的历史

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2024-12-18 DOI: 10.1002/prot.26780

Ryusei Matsumoto, Tomoaki Matsuura, Liam M Longo

{"title":"Distribution of Polyphosphate Kinase 2 Genes in Bacteria Underscores a Dynamic Evolutionary History.","authors":"Ryusei Matsumoto, Tomoaki Matsuura, Liam M Longo","doi":"10.1002/prot.26780","DOIUrl":"https://doi.org/10.1002/prot.26780","url":null,"abstract":"Polyphosphate kinase 2 (PPK2) enzymes catalyze phosphoryl transfer from polyphosphate to nucleotides and are divided into three classes, each presumed to have different catalytic preferences. With relevance to biotechnology, medicine, and primitive biology, there is significant interest in understanding the evolutionary history of PPK2 enzymes and predicting their functional properties. We reasoned that the distribution and pairing preferences of PPK2 gene classes across the prokaryote tree of life may shed light on these questions. PPK2 was found to be a dynamic gene family, often present in only a subset of species within a clade, even when considering a single genus. Although all possible PPK2 pairs were observed, a ~2-fold enrichment for Class I enzymes in species with multiple PPK2 genes strongly shapes pairing preferences. PPK2 class preference in the absence of PPK1, which synthesizes rather than utilizes polyphosphate, indicates the potential for functional adaptation and/or promiscuity with respect to reaction directionality for all classes, a feature that has previously been associated only with Class I. Patterns of adjacent PPK2 genes revealed signatures of gene duplication, as adjacent genes overwhelmingly belonged to the same class, as well as the potential for an added layer of PPK2 dynamics: hetero-oligomerization of single-domain Class II enzymes to recapitulate the structure of two-domain Class II enzymes. Finally, an updated PPK2 tree constructed from domains instead of genes calls into question established narratives of PPK2 evolution, putting new limits on the extent to which nucleobase promiscuity can be invoked in the early evolution of this family.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization and Inhibition of the Chaperone Function of Plasmodium falciparum Glucose-Regulated Protein 94 kDa (PfGrp94). 恶性疟原虫葡萄糖调节蛋白94kda （PfGrp94）伴侣蛋白功能的表征及抑制

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2024-12-13 DOI: 10.1002/prot.26779

Florence Lisa Muzenda, Melissa Louise Stofberg, Wendy Mthembu, Ikechukwu Achilonu, Erick Strauss, Tawanda Zininga

{"title":"Characterization and Inhibition of the Chaperone Function of Plasmodium falciparum Glucose-Regulated Protein 94 kDa (PfGrp94).","authors":"Florence Lisa Muzenda, Melissa Louise Stofberg, Wendy Mthembu, Ikechukwu Achilonu, Erick Strauss, Tawanda Zininga","doi":"10.1002/prot.26779","DOIUrl":"https://doi.org/10.1002/prot.26779","url":null,"abstract":"Plasmodium falciparum expresses four heat shock protein 90 (Hsp90) members. Among these, one, glucose-regulated protein 94 (PfGrp94), is localized in the endoplasmic reticulum (ER). Both the cytosolic and ER-based Hsp90s are essential for parasite survival under all growth conditions. The cytosolic version has been extensively studied and has been targeted in several efforts through the repurposing of anticancer therapeutics as antimalarial drugs. However, PfGrp94 has not been fully characterized and some of its functions related to the ER stress response are not fully understood. Structural analysis of the recombinant full-length PfGrp94 protein showed a predominantly α-helical secondary structure and its thermal resilience was modulated by 5'-N-ethyl-carboxamide-adenosine (NECA) and nucleotides ATP/ADP. PfGrp94 exhibits ATPase activity and suppressed heat-induced aggregation of a model substrate, malate dehydrogenase, in a nucleotide-dependent manner. However, these PfGrp94 chaperone functions were abrogated by NECA. Molecular docking and molecular dynamics (MD) simulations showed that NECA interacted with unique residues on PfGrp94, which could be potentially exploited for selective drug design. Finally, using parasites maintained at the red blood stage, NECA exhibited moderate antiplasmodial activity (IC50 of 4.3, 7.4, and 10.0 μM) against three different P. falciparum strains. Findings from this study provide the first direct evidence for the correlation between in silico, biochemical, and in vitro data toward utilizing the ER-based chaperone, PfGrp94, as a drug target against the malaria parasites.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural Basis for Monomer-Dimer Transition of Dri1 Upon Heme Binding. 血红素结合时 Dri1 单体-二聚体转变的结构基础

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2024-12-13 DOI: 10.1002/prot.26778

Xiao-Ying Wang, Jing Zhang, Hong-Yan Li, Chen-Song Dong, Huai-En Dai, Mingzhu Wang, Lin Liu

引用次数: 0

MuGger Toxins: Exploring the Selective Binding Mechanism of Clostridial Glucosyltransferase Toxin B and Host GTPases. MuGger毒素：探索梭菌糖基转移酶毒素B与宿主gtp酶的选择性结合机制。

IF 3.2 4区生物学

Proteins-Structure Function and Bioinformatics Pub Date : 2024-12-13 DOI: 10.1002/prot.26770

Damla Nur Camli, Haci Aslan Onur Iscil, Saliha Ece Acuner

{"title":"MuGger Toxins: Exploring the Selective Binding Mechanism of Clostridial Glucosyltransferase Toxin B and Host GTPases.","authors":"Damla Nur Camli, Haci Aslan Onur Iscil, Saliha Ece Acuner","doi":"10.1002/prot.26770","DOIUrl":"https://doi.org/10.1002/prot.26770","url":null,"abstract":"(a) Clostridioides difficile (C. difficile) bacterium can cause severe diarrhea and its over-colonization in the host's intestinal tract lead to the development of pseudomembranous colitis, generally due to antibiotic usage. The primary exotoxins involved are toxin A (TcdA) and toxin B (TcdB), the latter being more pathogenic. TcdB has glucosyltransferase activity and mediates monoglycosylation by targeting host cell enzymes (mainly Rho and Ras family of GTPases) with differential selectivity. Here, we aim to provide structural and dynamic insights into how TcdB impacts the host's intestinal epithelial cells focusing on the glycosylation mechanism of Rho GTPases, Cdc42, and Rac1, at the molecular level. To this aim, we modeled the unknown TcdB-host protein complex structures, based on the available experimental structures of TcdB, through protein-protein docking. Then, we elaborated on TcdB-Rho GTPase models as TcdB is known to selectively interact with GDP-bound inactive states of Rho GTPases, over the GTP-bound active ones, but the mechanism is unclear. Through a total of 6 μs-long molecular dynamics simulation of TcdB and GTP/GDP-bound Rac1 and Cdc42 complexes, TcdB's selective binding mechanism was revealed for Rac1. TcdB-Rac1 complexes were further analyzed with enhanced sampling techniques such as well-tempered metadynamics simulations and umbrella sampling to reveal selective binding mechanism between TcdB and GDP-bound Rac1. Our results show that TcdB selectively binds to GDP-bound Rac1, over the GTP-bound one, driven by its affinity for the Mg2+ ion. A destabilized Mg2+ ion incapable of coordinating GDP disrupts Rac1's GTPase function, shedding light on the molecular basis of TcdB's pathogenic effects.","PeriodicalId":56271,"journal":{"name":"Proteins-Structure Function and Bioinformatics","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142820248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0