Vuillemot Rémi, Miyashita Osamu, Tama Florence, Rouiller Isabelle, Jonic Slavica
IMPMC - UMR 7590 CNRS, Sorbonne Université, Muséum National d'Histoire Naturelle, Paris, France; Department of Biochemistry & Pharmacology and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Victoria, Australia. Electronic address: https://twitter.com/@RemiVuillemot.
RIKEN Center for Computational Science, Japan.
J Mol Biol. 2022 Apr 15;434(7):167483. doi: 10.1016/j.jmb.2022.167483. Epub 2022 Feb 9.
Atomic models of cryo electron microscopy (cryo-EM) maps of biomolecular conformations are often obtained by flexible fitting of the maps with available atomic structures of other conformations (e.g., obtained by X-ray crystallography). This article presents a new flexible fitting method, NMMD, which combines normal mode analysis (NMA) and molecular dynamics simulation (MD). Given an atomic structure and a cryo-EM map to fit, NMMD simultaneously estimates global atomic displacements based on NMA and local displacements based on MD. NMMD was implemented by modifying EMfit, a flexible fitting method using MD only, in GENESIS 1.4. As EMfit, NMMD can be run with replica exchange umbrella sampling procedure. The new method was tested using a variety of EM maps (synthetic and experimental, with different noise levels and resolutions). The results of the tests show that adding normal modes to MD-based fitting makes the fitting faster (40% in average) and, in the majority of cases, more accurate.
生物分子构象的冷冻电子显微镜（cryo-EM）图谱的原子模型通常是通过将图谱与其他构象的可用原子结构（例如通过X射线晶体学获得的结构）进行灵活拟合得到的。本文提出了一种新的灵活拟合方法NMMD，它结合了简正模式分析（NMA）和分子动力学模拟（MD）。给定一个原子结构和一个要拟合的cryo-EM图谱，NMMD同时基于NMA估计全局原子位移，并基于MD估计局部位移。NMMD是通过在GENESIS 1.4中修改仅使用MD的灵活拟合方法EMfit来实现的。与EMfit一样，NMMD可以使用副本交换伞形采样程序运行。使用各种EM图谱（合成的和实验的，具有不同的噪声水平和分辨率）对新方法进行了测试。测试结果表明，在基于MD的拟合中加入简正模式可以使拟合速度更快（平均快40%），并且在大多数情况下更准确。
