Proteins: Structure最新文献_第10页

Coarse‐grained and atomic resolution biomolecular docking with the ATTRACT approach 与吸引方法进行粗粒度和原子分辨率的生物分子对接

Proteins: Structure Pub Date : 2019-11-30 DOI: 10.1002/prot.25860

G. Glashagen, S. D. de Vries, Urszula Uciechowska-Kaczmarzyk, S. Samsonov, S. Murail, P. Tufféry, M. Zacharias

引用次数: 7

Structure prediction of biological assemblies using GALAXY in CAPRI rounds 38‐45 在CAPRI第38 - 45轮中使用GALAXY进行生物组装体的结构预测

Proteins: Structure Pub Date : 2019-11-27 DOI: 10.1002/prot.25859

Taeyong Park, Hyeonuk Woo, M. Baek, Jinsol Yang, Chaok Seok

{"title":"Structure prediction of biological assemblies using GALAXY in CAPRI rounds 38‐45","authors":"Taeyong Park, Hyeonuk Woo, M. Baek, Jinsol Yang, Chaok Seok","doi":"10.1002/prot.25859","DOIUrl":"https://doi.org/10.1002/prot.25859","url":null,"abstract":"We participated in CARPI rounds 38‐45 both as a server predictor and a human predictor. These CAPRI rounds provided excellent opportunities for testing prediction methods for three classes of protein interactions, that is, protein‐protein, protein‐peptide, and protein‐oligosaccharide interactions. Both template‐based methods (GalaxyTBM for monomer protein, GalaxyHomomer for homo‐oligomer protein, GalaxyPepDock for protein‐peptide complex) and ab initio docking methods (GalaxyTongDock and GalaxyPPDock for protein oligomer, GalaxyPepDock‐ab‐initio for protein‐peptide complex, GalaxyDock2 and Galaxy7TM for protein‐oligosaccharide complex) have been tested. Template‐based methods depend heavily on the availability of proper templates and template‐target similarity, and template‐target difference is responsible for inaccuracy of template‐based models. Inaccurate template‐based models could be improved by our structure refinement and loop modeling methods based on physics‐based energy optimization (GalaxyRefineComplex and GalaxyLoop) for several CAPRI targets. Current ab initio docking methods require accurate protein structures as input. Small conformational changes from input structure could be accounted for by our docking methods, producing one of the best models for several CAPRI targets. However, predicting large conformational changes involving protein backbone is still challenging, and full exploration of physics‐based methods for such problems is still to come.","PeriodicalId":20789,"journal":{"name":"Proteins: Structure","volume":"97 1","pages":"1009 - 1017"},"PeriodicalIF":0.0,"publicationDate":"2019-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74983497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Integrative modeling of protein‐protein interactions with pyDock for the new docking challenges 基于pyDock的蛋白质-蛋白质相互作用的综合建模，以应对新的对接挑战

Proteins: Structure Pub Date : 2019-11-19 DOI: 10.1002/prot.25858

Mireia Rosell, Luis A Rodríguez-Lumbreras, Miguel Romero-Durana, Brian Jiménez‐García, Lucía Díaz, J. Fernández-Recio

{"title":"Integrative modeling of protein‐protein interactions with pyDock for the new docking challenges","authors":"Mireia Rosell, Luis A Rodríguez-Lumbreras, Miguel Romero-Durana, Brian Jiménez‐García, Lucía Díaz, J. Fernández-Recio","doi":"10.1002/prot.25858","DOIUrl":"https://doi.org/10.1002/prot.25858","url":null,"abstract":"The seventh CAPRI edition imposed new challenges to the modeling of protein‐protein complexes, such as multimeric oligomerization, protein‐peptide, and protein‐oligosaccharide interactions. Many of the proposed targets needed the efficient integration of rigid‐body docking, template‐based modeling, flexible optimization, multiparametric scoring, and experimental restraints. This was especially relevant for the multimolecular assemblies proposed in the CASP12‐CAPRI37 and CASP13‐CAPRI46 joint rounds, which were described and evaluated elsewhere. Focusing on the purely CAPRI targets of this edition (rounds 38‐45), we have participated in all 17 assessed targets (considering heteromeric and homomeric interfaces in T125 as two separate targets) both as predictors and as scorers, by using integrative modeling based on our docking and scoring approaches: pyDock, IRaPPA, and LightDock. In the protein‐protein and protein‐peptide targets, we have also participated with our webserver (pyDockWeb). On these 17 CAPRI targets, we submitted acceptable models (or better) within our top 10 models for 10 targets as predictors, 13 targets as scorers, and 4 targets as servers. In summary, our participation in this CAPRI edition confirmed the capabilities of pyDock for the scoring of docking models, increasingly used within the context of integrative modeling of protein interactions and multimeric assemblies.","PeriodicalId":20789,"journal":{"name":"Proteins: Structure","volume":"45 1","pages":"1008 - 999"},"PeriodicalIF":0.0,"publicationDate":"2019-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89762533","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Escapement mechanisms: Efficient free energy transduction by reciprocally‐coupled gating 擒纵机构:通过往复耦合门控有效的自由能转导

Proteins: Structure Pub Date : 2019-11-19 DOI: 10.1002/prot.25856

C. Carter

{"title":"Escapement mechanisms: Efficient free energy transduction by reciprocally‐coupled gating","authors":"C. Carter","doi":"10.1002/prot.25856","DOIUrl":"https://doi.org/10.1002/prot.25856","url":null,"abstract":"Conversion of the free energy of NTP hydrolysis efficiently into mechanical work and/or information by transducing enzymes sustains living systems far from equilibrium, and so has been of interest for many decades. Detailed molecular mechanisms, however, remain puzzling and incomplete. We previously reported that catalysis of tryptophan activation by tryptophanyl‐tRNA synthetase, TrpRS, requires relative domain motion to re‐position the catalytic Mg2+ ion, noting the analogy between that conditional hydrolysis of ATP and the escapement mechanism of a mechanical clock. The escapement allows the time‐keeping mechanism to advance discretely, one gear at a time, if and only if the pendulum swings, thereby converting energy from the weight driving the pendulum into rotation of the hands. Coupling of catalysis to domain motion, however, mimics only half of the escapement mechanism, suggesting that domain motion may also be reciprocally coupled to catalysis, completing the escapement metaphor. Computational studies of the free energy surface restraining the domain motion later confirmed that reciprocal coupling: the catalytic domain motion is thermodynamically unfavorable unless the PPi product is released from the active site. These two conditional phenomena—demonstrated together only for the TrpRS mechanism—function as reciprocally‐coupled gates. As we and others have noted, such an escapement mechanism is essential to the efficient transduction of NTP hydrolysis free energy into other useful forms of mechanical or chemical work and/or information. Some implementation of both gating mechanisms—catalysis by domain motion and domain motion by catalysis—will thus likely be found in many other systems.","PeriodicalId":20789,"journal":{"name":"Proteins: Structure","volume":"132 1","pages":"710 - 717"},"PeriodicalIF":0.0,"publicationDate":"2019-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74203655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 16

Docking proteins and peptides under evolutionary constraints in Critical Assessment of PRediction of Interactions rounds 38 to 45 在相互作用预测的关键评估中，在进化约束下对接蛋白质和肽第38至45轮

Proteins: Structure Pub Date : 2019-11-19 DOI: 10.1002/prot.25857

A. Nadaradjane, Chloé Quignot, S. Traoré, J. Andreani, R. Guérois

{"title":"Docking proteins and peptides under evolutionary constraints in Critical Assessment of PRediction of Interactions rounds 38 to 45","authors":"A. Nadaradjane, Chloé Quignot, S. Traoré, J. Andreani, R. Guérois","doi":"10.1002/prot.25857","DOIUrl":"https://doi.org/10.1002/prot.25857","url":null,"abstract":"Computational structural prediction of macromolecular interactions is a fundamental tool toward the global understanding of cellular processes. The Critical Assessment of PRediction of Interactions (CAPRI) community‐wide experiment provides excellent opportunities for blind testing computational docking methods and includes original targets, thus widening the range of docking applications. Our participation in CAPRI rounds 38 to 45 enabled us to expand the way we include evolutionary information in structural predictions beyond our standard free docking InterEvDock pipeline. InterEvDock integrates a coarse‐grained potential that accounts for interface coevolution based on joint multiple sequence alignments of two protein partners (co‐alignments). However, even though such co‐alignments could be built for none of the CAPRI targets in rounds 38 to 45, including host‐pathogen and protein‐oligosaccharide complexes and a redesigned interface, we identified multiple strategies that can be used to incorporate evolutionary constraints, which helped us to identify the most likely macromolecular binding modes. These strategies include template‐based modeling where only local adjustments should be applied when query‐template sequence identity is above 30% and larger perturbations are needed below this threshold; covariation‐based structure prediction for individual protein partners; and the identification of evolutionarily conserved and structurally recurrent anchoring interface motifs. Overall, we submitted correct predictions among the top 5 models for 12 out of 19 interface challenges, including four High‐ and five Medium‐quality predictions. Our top 20 models included correct predictions for three out of the five targets we missed in the top 5, including two targets for which misleading biological data led us to downgrade correct free docking models.","PeriodicalId":20789,"journal":{"name":"Proteins: Structure","volume":"40 1","pages":"986 - 998"},"PeriodicalIF":0.0,"publicationDate":"2019-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75160990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Issue Information ‐ Table of Content 发行信息‐内容表

Proteins: Structure Pub Date : 2019-11-11 DOI: 10.1002/prot.25567

引用次数: 0

Computational simulations of TNF receptor oligomerization on plasma membrane TNF受体在质膜上寡聚化的计算模拟

Proteins: Structure Pub Date : 2019-11-11 DOI: 10.1002/prot.25854

Zhaoqian Su, Yinghao Wu

{"title":"Computational simulations of TNF receptor oligomerization on plasma membrane","authors":"Zhaoqian Su, Yinghao Wu","doi":"10.1002/prot.25854","DOIUrl":"https://doi.org/10.1002/prot.25854","url":null,"abstract":"The interactions between tumor necrosis factors (TNFs) and their corresponding receptors (TNFRs) play a pivotal role in inflammatory responses. Upon ligand binding, TNFR receptors were found to form oligomers on cell surfaces. However, the underlying mechanism of oligomerization is not fully understood. In order to tackle this problem, molecular dynamics (MD) simulations have been applied to the complex between TNF receptor‐1 (TNFR1) and its ligand TNF‐α as a specific test system. The simulations on both all‐atom (AA) and coarse‐grained (CG) levels achieved the similar results that the extracellular domains of TNFR1 can undergo large fluctuations on plasma membrane, while the dynamics of TNFα‐TNFR1 complex is much more constrained. Using the CG model with the Martini force field, we are able to simulate the systems that contain multiple TNFα‐TNFR1 complexes with the timescale of microseconds. We found that complexes can aggregate into oligomers on the plasma membrane through the lateral interactions between receptors at the end of the CG simulations. We suggest that this spatial organization is essential to the efficiency of signal transduction for ligands that belong to the TNF superfamily. We further show that the aggregation of two complexes is initiated by the association between the N‐terminal domains of TNFR1 receptors. Interestingly, the cis‐interfaces between N‐terminal regions of two TNF receptors have been observed in the previous X‐ray crystallographic experiment. Therefore, we provide supportive evidence that cis‐interface is of functional importance in triggering the receptor oligomerization. Taken together, our study brings insights to understand the molecular mechanism of TNF signaling.","PeriodicalId":20789,"journal":{"name":"Proteins: Structure","volume":"50 1","pages":"698 - 709"},"PeriodicalIF":0.0,"publicationDate":"2019-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79233300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

Learning a functional grammar of protein domains using natural language word embedding techniques 使用自然语言词嵌入技术学习蛋白质域的功能语法

Proteins: Structure Pub Date : 2019-11-08 DOI: 10.1002/prot.25842

Daniel W. A. Buchan, David T. Jones

引用次数: 12

Design and characterization of novel dual Fc antibody with enhanced avidity for Fc receptors 增强Fc受体亲和度的新型双Fc抗体的设计与鉴定

Proteins: Structure Pub Date : 2019-11-08 DOI: 10.1002/prot.25853

Dennis R. Goulet, A. Zwolak, James A. Williams, M. Chiu, W. Atkins

{"title":"Design and characterization of novel dual Fc antibody with enhanced avidity for Fc receptors","authors":"Dennis R. Goulet, A. Zwolak, James A. Williams, M. Chiu, W. Atkins","doi":"10.1002/prot.25853","DOIUrl":"https://doi.org/10.1002/prot.25853","url":null,"abstract":"Monoclonal antibodies (mAbs) have become an important class of therapeutics, particularly in the realm of anticancer immunotherapy. While the two antigen‐binding fragments (Fabs) of an mAb allow for high‐avidity binding to molecular targets, the crystallizable fragment (Fc) engages immune effector elements. mAbs of the IgG class are used for the treatment of autoimmune diseases and can elicit antitumor immune functions not only by several mechanisms including direct antigen engagement via their Fab arms but also by Fab binding to tumors combined with Fc engagement of complement component C1q and Fcγ receptors. Additionally, IgG binding to the neonatal Fc receptor (FcRn) allows for endosomal recycling and prolonged serum half‐life. To augment the effector functions or half‐life of an IgG1 mAb, we constructed a novel “2Fc” mAb containing two Fc domains in addition to the normal two Fab domains. Structural and functional characterization of this 2Fc mAb demonstrated that it exists in a tetrahedral‐like geometry and retains binding capacity via the Fab domains. Furthermore, duplication of the Fc region significantly enhanced avidity for Fc receptors FcγRI, FcγRIIIa, and FcRn, which manifested as a decrease in complex dissociation rate that was more pronounced at higher densities of receptor. At intermediate receptor density, the dissociation rate for Fc receptors was decreased 6‐ to 130‐fold, resulting in apparent affinity increases of 7‐ to 42‐fold. Stoichiometric analysis confirmed that each 2Fc mAb may simultaneously bind two molecules of FcγRI or four molecules of FcRn, which is double the stoichiometry of a wild‐type mAb. In summary, duplication of the IgG Fc region allows for increased avidity to Fc receptors that could translate into clinically relevant enhancement of effector functions or pharmacokinetics.","PeriodicalId":20789,"journal":{"name":"Proteins: Structure","volume":"1 1","pages":"689 - 697"},"PeriodicalIF":0.0,"publicationDate":"2019-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89348575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Performance and enhancement of the LZerD protein assembly pipeline in CAPRI 38‐46 CAPRI 38‐46中LZerD蛋白组装管道的性能和增强

Proteins: Structure Pub Date : 2019-11-07 DOI: 10.1002/prot.25850

Charles W Christoffer, Genki Terashi, Woong-Hee Shin, Tunde Aderinwale, Sai Raghavendra Maddhuri Venkata Subraman, Lenna X. Peterson, Jacob Verburgt, D. Kihara

{"title":"Performance and enhancement of the LZerD protein assembly pipeline in CAPRI 38‐46","authors":"Charles W Christoffer, Genki Terashi, Woong-Hee Shin, Tunde Aderinwale, Sai Raghavendra Maddhuri Venkata Subraman, Lenna X. Peterson, Jacob Verburgt, D. Kihara","doi":"10.1002/prot.25850","DOIUrl":"https://doi.org/10.1002/prot.25850","url":null,"abstract":"We report the performance of the protein docking prediction pipeline of our group and the results for Critical Assessment of Prediction of Interactions (CAPRI) rounds 38‐46. The pipeline integrates programs developed in our group as well as other existing scoring functions. The core of the pipeline is the LZerD protein‐protein docking algorithm. If templates of the target complex are not found in PDB, the first step of our docking prediction pipeline is to run LZerD for a query protein pair. Meanwhile, in the case of human group prediction, we survey the literature to find information that can guide the modeling, such as protein‐protein interface information. In addition to any literature information and binding residue prediction, generated docking decoys were selected by a rank aggregation of statistical scoring functions. The top 10 decoys were relaxed by a short molecular dynamics simulation before submission to remove atom clashes and improve side‐chain conformations. In these CAPRI rounds, our group, particularly the LZerD server, showed robust performance. On the other hand, there are failed cases where some other groups were successful. To understand weaknesses of our pipeline, we analyzed sources of errors for failed targets. Since we noted that structure refinement is a step that needs improvement, we newly performed a comparative study of several refinement approaches. Finally, we show several examples that illustrate successful and unsuccessful cases by our group.","PeriodicalId":20789,"journal":{"name":"Proteins: Structure","volume":"69 1","pages":"948 - 961"},"PeriodicalIF":0.0,"publicationDate":"2019-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86898960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 10