• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Journal of Molecular Biology >EvoDesign: Designing Protein-Protein Binding Interactions Using Evolutionary Interface Profiles in Conjunction with an Optimized Physical Energy Function
【24h】

EvoDesign: Designing Protein-Protein Binding Interactions Using Evolutionary Interface Profiles in Conjunction with an Optimized Physical Energy Function

机译：挖掘：使用进化界面型材结合优化的物理能量功能设计蛋白质 - 蛋白质结合相互作用

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

EvoDesign (https://zhanglab.ccmb.med.umich.edu/EvoDesign) is an online server system for protein design. The method uses evolutionary profiles to guide the sequence search simulation and demonstrated significant advantages over physics-based approaches in terms of more accurately designing proteins that adopt desired target folds. Despite the success, the previous EvoDesign program focused only on monomer protein design, which limited its ability and usefulness in terms of designing functional proteins. In this work, we propose a new EvoDesign server, which extends the principles of evolution-based design to design protein protein interactions. Starting from a two-chain complex structure, structurally similar interfaces are identified from known protein-protein interaction databases. An interface evolutionary profile is then constructed from a multiple sequence alignment of the interface analogies, which is combined with a newly developed, atomic-level physical energy function to guide the replica-exchange Monte Carlo simulation search. The purpose of the server is to redesign the specified complex chain to increase its stability and binding affinity for the other chain in the complex. With the improved scope and accuracy of the methodology, the new EvoDesign pipeline should become a useful online tool for functional protein design and drug discovery studies. (C) 2019 Elsevier Ltd. All rights reserved.
机译：evodeSign（https://zhanglab.ccmb.med.umich.edu/evodesign）是蛋白质设计的在线服务器系统。该方法采用进化配置文件来指导序列搜索仿真，并在更准确地设计采用所需目标折叠的蛋白质方面对基于物理的方法进行了显着的优势。尽管成功，以前的展示程序仅集中在单体蛋白质设计上，这限制了其在设计功能蛋白方面的能力和有用性。在这项工作中，我们提出了一个新的EvodeSign服务器，它扩展了基于进化的设计原则来设计蛋白质蛋白质相互作用。从双链复合结构开始，结构相似的接口是从已知的蛋白质 - 蛋白质相互作用数据库中鉴定的。然后由界面进化的界面模拟的多个序列对准构成，该界面类比与新开发的原子级物理能量功能组合以引导副本交换蒙特卡罗模拟搜索。服务器的目的是重新设计指定的复杂链以增加其在复杂的其他链中的稳定性和绑定亲和力。随着方法的改进范围和准确性，新的EvodeSign管道应该成为功能蛋白设计和药物发现研究的有用的在线工具。 （c）2019 Elsevier Ltd.保留所有权利。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号