Extracting time series matching a small-angle X-ray scattering profile from trajectories of molecular dynamics simulations

• Published in: Scientific reports Vol. 12; no. 1; pp. 9970 - 13
• Main Authors: Shimizu, Masahiro, Okuda, Aya, Morishima, Ken, Inoue, Rintaro, Sato, Nobuhiro, Yunoki, Yasuhiro, Urade, Reiko, Sugiyama, Masaaki
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.06.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/57; 631/57/2266; 631/57/2282; Computer applications; Humanities and Social Sciences; multidisciplinary; Protein structure; Science; Science (multidisciplinary); Simulation; Time series; X-ray scattering
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-13982-9

Solving structural ensembles of flexible biomolecules is a challenging research area. Here, we propose a method to obtain possible structural ensembles of a biomolecule based on small-angle X-ray scattering (SAXS) and molecular dynamics simulations. Our idea is to clip a time series that matches a SAXS profile from a simulation trajectory. To examine its practicability, we applied our idea to a multi-domain protein ER-60 and successfully extracted time series longer than 1 micro second from trajectories of coarse-grained molecular dynamics simulations. In the extracted time series, the domain conformation was distributed continuously and smoothly in a conformational space. Preferred domain conformations were also observed. Diversity among scattering curves calculated from each ER-60 structure was interpreted to reflect an open-close motion of the protein. Although our approach did not provide a unique solution for the structural ensemble of the biomolecule, each extracted time series can be an element of the real behavior of ER-60. Considering its low computational cost, our approach will play a key role to identify biomolecular dynamics by integrating SAXS, simulations, and other experiments.