在硅筛选蛋白质的灵活性

H. Gohlke, Hannes Kopitz
{"title":"在硅筛选蛋白质的灵活性","authors":"H. Gohlke, Hannes Kopitz","doi":"10.1002/0471266949.BMC148","DOIUrl":null,"url":null,"abstract":"We summarize computational approaches in structure-based ligand design (SBLD) and in silico screening that address issues of protein flexibility and mobility. In particular, we consider how protein plasticity can be incorporated into docking strategies. As a first requirement, one needs to detect what can move and how. Moving protein parts can be identified from experimental information as well as established computational techniques such as molecular dynamics (MD) simulations, graph theoretical and geometry-based approaches, or harmonic analysis-based methods. Second, this knowledge needs to be transformed into a docking algorithm. A multitude of approaches considering protein mobility has been introduced recently, with motions modeled either implicitly or explicitly. In the latter case, one can further distinguish between modeling of side-chain-only motions and motions including backbone changes. In all cases, accuracy needs to be balanced against efficiency. Case studies for which the inclusion of protein plasticity was crucial to success are noted along these lines. This allows us to identify scope and limitations of the current approaches, as well as guidelines for further developments. \n \n \nKeywords: \n \nconformational selection; \nconformational variability; \nflexible docking; \nflexibility; \ninduced fit; \nmobility; \nplasticity; \nprotein–ligand","PeriodicalId":9514,"journal":{"name":"Burger's Medicinal Chemistry and Drug Discovery","volume":"79 1","pages":"867-887"},"PeriodicalIF":0.0000,"publicationDate":"2010-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Protein Flexibility in In Silico Screening\",\"authors\":\"H. Gohlke, Hannes Kopitz\",\"doi\":\"10.1002/0471266949.BMC148\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"We summarize computational approaches in structure-based ligand design (SBLD) and in silico screening that address issues of protein flexibility and mobility. In particular, we consider how protein plasticity can be incorporated into docking strategies. As a first requirement, one needs to detect what can move and how. Moving protein parts can be identified from experimental information as well as established computational techniques such as molecular dynamics (MD) simulations, graph theoretical and geometry-based approaches, or harmonic analysis-based methods. Second, this knowledge needs to be transformed into a docking algorithm. A multitude of approaches considering protein mobility has been introduced recently, with motions modeled either implicitly or explicitly. In the latter case, one can further distinguish between modeling of side-chain-only motions and motions including backbone changes. In all cases, accuracy needs to be balanced against efficiency. Case studies for which the inclusion of protein plasticity was crucial to success are noted along these lines. This allows us to identify scope and limitations of the current approaches, as well as guidelines for further developments. \\n \\n \\nKeywords: \\n \\nconformational selection; \\nconformational variability; \\nflexible docking; \\nflexibility; \\ninduced fit; \\nmobility; \\nplasticity; \\nprotein–ligand\",\"PeriodicalId\":9514,\"journal\":{\"name\":\"Burger's Medicinal Chemistry and Drug Discovery\",\"volume\":\"79 1\",\"pages\":\"867-887\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2010-09-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Burger's Medicinal Chemistry and Drug Discovery\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1002/0471266949.BMC148\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Burger's Medicinal Chemistry and Drug Discovery","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/0471266949.BMC148","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

我们总结了基于结构的配体设计(SBLD)和硅筛选中解决蛋白质灵活性和流动性问题的计算方法。特别是,我们考虑如何将蛋白质可塑性纳入对接策略。作为第一个要求,我们需要检测什么可以移动以及如何移动。移动的蛋白质部分可以从实验信息以及已建立的计算技术(如分子动力学(MD)模拟,图理论和基于几何的方法,或基于谐波分析的方法)中识别。其次,需要将这些知识转化为对接算法。最近引入了许多考虑蛋白质迁移的方法,其中包括隐式或显式的运动模型。在后一种情况下,可以进一步区分仅侧链运动的建模和包含骨干变化的运动的建模。在所有情况下,准确性都需要与效率相平衡。在这些研究中,蛋白质的可塑性对成功至关重要。这使我们能够确定当前方法的范围和局限性,以及进一步发展的指导方针。关键词:构象选择;构象变化;灵活对接;灵活性;诱导契合;流动性;可塑性;protein-ligand
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Protein Flexibility in In Silico Screening
We summarize computational approaches in structure-based ligand design (SBLD) and in silico screening that address issues of protein flexibility and mobility. In particular, we consider how protein plasticity can be incorporated into docking strategies. As a first requirement, one needs to detect what can move and how. Moving protein parts can be identified from experimental information as well as established computational techniques such as molecular dynamics (MD) simulations, graph theoretical and geometry-based approaches, or harmonic analysis-based methods. Second, this knowledge needs to be transformed into a docking algorithm. A multitude of approaches considering protein mobility has been introduced recently, with motions modeled either implicitly or explicitly. In the latter case, one can further distinguish between modeling of side-chain-only motions and motions including backbone changes. In all cases, accuracy needs to be balanced against efficiency. Case studies for which the inclusion of protein plasticity was crucial to success are noted along these lines. This allows us to identify scope and limitations of the current approaches, as well as guidelines for further developments. Keywords: conformational selection; conformational variability; flexible docking; flexibility; induced fit; mobility; plasticity; protein–ligand
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信