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

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.