Faculty of Chemistry, University of Gdańsk, Gdańsk 80-308, Poland.
Institute of Physics, Polish Academy of Sciences, Warsaw 02-668, Poland.
Bioinformatics. 2021 Jul 12;37(11):1613-1615. doi: 10.1093/bioinformatics/btaa897.
The majority of the proteins in living organisms occur as homo- or hetero-multimeric structures. Although there are many tools to predict the structures of single-chain proteins or protein complexes with small ligands, peptide-protein and protein-protein docking is more challenging. In this work, we utilized multiplexed replica-exchange molecular dynamics (MREMD) simulations with the physics-based heavily coarse-grained UNRES model, which provides more than a 1000-fold simulation speed-up compared with all-atom approaches to predict structures of protein complexes.
We present a new protein-protein and peptide-protein docking functionality of the UNRES package, which includes a variable degree of conformational flexibility. UNRES-Dock protocol was tested on a set of 55 complexes with size from 43 to 587 amino-acid residues, showing that structures of the complexes can be predicted with good quality, if the sampling of the conformational space is sufficient, especially for flexible peptide-protein systems. The developed automatized protocol has been implemented in the standalone UNRES package and in the UNRES server.
UNRES server: http://unres-server.chem.ug.edu.pl; UNRES package and data used in testing of UNRES-Dock: http://unres.pl.
Supplementary data are available at Bioinformatics online.
生物体中的大多数蛋白质都以同型或异型多聚体结构存在。尽管有许多工具可以预测单链蛋白质或与小分子配体结合的蛋白质复合物的结构，但肽-蛋白质和蛋白质-蛋白质对接更具挑战性。在这项工作中，我们利用基于物理的重度粗粒化 UNRES 模型的多重置换分子动力学（MREMD）模拟，与全原子方法相比，该模型提供了超过 1000 倍的模拟加速，以预测蛋白质复合物的结构。
我们提出了 UNRES 包的新的蛋白质-蛋白质和肽-蛋白质对接功能，其中包括一定程度的构象灵活性。UNRES-Dock 协议在一组大小为 43 到 587 个氨基酸残基的 55 个复合物上进行了测试，结果表明，如果构象空间的采样足够充分，则可以很好地预测复合物的结构，特别是对于灵活的肽-蛋白质系统。开发的自动化协议已在独立的 UNRES 包和 UNRES 服务器中实现。
UNRES 服务器：http://unres-server.chem.ug.edu.pl；用于测试 UNRES-Dock 的 UNRES 包和数据：http://unres.pl。
补充数据可在生物信息学在线获得。
