Georg-August-Universität, Göttingen, Germany.
Theoretical Physics and Center for Biophysics, Saarland University, Saarbrücken, Germany.
Methods Mol Biol. 2020;2168:199-215. doi: 10.1007/978-1-0716-0724-4_9.
Small- and wide-angle X-ray scattering (SAXS/WAXS/SWAXS) have evolved to be accurate tools used to gain structural information of biomolecules in solution. However, the interpretation of SWAXS data remains challenging owing to the low information content of the data and scattering contributions from the solvent. In recent years, methods for the interpretation of SWAXS data based on explicit-solvent molecular dynamics (MD) simulations have become increasingly popular. The physicochemical information in the MD force fields complements the low-information SWAXS data, thereby greatly reducing the risk of overfitting, and the explicit-solvent models may accurately account for scattering contributions from the solvent. In this chapter, we provide a practical introduction to MD-based methods for the interpretation of SWAXS data. First, we present the back-calculation of a SWAXS curve from an MD trajectory as required to validate an MD simulation against experimental SWAXS data. Second, we present the structure refinement of an atomic model against SWAXS data using SAXS-driven MD simulations. Common technical problems together with appropriate solutions are discussed.
小角和广角 X 射线散射（SAXS/WAXS/SWAXS）已经发展成为用于获取溶液中生物分子结构信息的准确工具。然而，由于数据信息量低和溶剂的散射贡献，SWAXS 数据的解释仍然具有挑战性。近年来，基于显式溶剂分子动力学（MD）模拟的 SWAXS 数据解释方法变得越来越流行。MD 力场中的物理化学信息补充了低信息量的 SWAXS 数据，从而大大降低了过度拟合的风险，并且显式溶剂模型可以准确地解释溶剂的散射贡献。在本章中，我们提供了一种基于 MD 方法的实用介绍，用于解释 SWAXS 数据。首先，我们展示了从 MD 轨迹反推 SWAXS 曲线的过程，这是验证 MD 模拟与实验 SWAXS 数据吻合的必要步骤。其次，我们展示了使用 SAXS 驱动的 MD 模拟对原子模型进行 SWAXS 数据结构精修的过程。讨论了常见的技术问题及相应的解决方案。
