Analysis of conformational stability of interacting residues in protein binding interfaces.
Analysis of conformational stability of interacting residues in protein binding interfaces.
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蛋白质结合界面中相互作用残基的构象稳定性分析。
DOI：
10.1093/protein/gzad016
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Pantazes,RobertJ
中科院分区：
文献类型：
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作者：
Chauhan,VarunM;Pantazes,RobertJ
经过大约60年的工作，蛋白质折叠问题最近取得了快速进展，这要归功于AlphaFold和RoseTTAFold的发明，这两种机器学习算法能够根据它们的序列可靠地预测蛋白质结构。他们成功的一个关键组成部分是纳入了残基之间的成对相互作用信息。随着研究重点转向开发算法来设计和设计结合蛋白质，了解蛋白质界面的相互作用特征可能会改善预测。在这里，我们分析了574个蛋白质复合体，以确定它们两两相互作用的稳定性特征，揭示了预稳定残基之间的相互作用是蛋白质结合界面的一个选定特征。在一项对475de新设计结合蛋白的回顾分析中，实验成功率为19%，包括成对相互作用预稳定参数将识别实验成功结合蛋白的频率提高到40%。
After approximately 60 years of work, the protein folding problem has recently seen rapid advancement thanks to the inventions of AlphaFold and RoseTTAFold, which are machine-learning algorithms capable of reliably predicting protein structures from their sequences. A key component in their success was the inclusion of pairwise interaction information between residues. As research focus shifts towards developing algorithms to design and engineer binding proteins, it is likely that knowledge of interaction features at protein interfaces can improve predictions. Here, 574 protein complexes were analyzed to identify the stability features of their pairwise interactions, revealing that interactions between pre-stabilized residues are a selected feature in protein binding interfaces. In a retrospective analysis of 475de novodesigned binding proteins with an experimental success rate of 19%, inclusion of pairwise interaction pre-stabilization parameters increased the frequency of identifying experimentally successful binders to 40%.