Integrating solvation shell structure in experimentally driven molecular dynamics using x-ray solution scattering data
Integrating solvation shell structure in experimentally driven molecular dynamics using x-ray solution scattering data
复制标题
DOI：
10.1063/5.0007158
复制
发表时间：
2020-05-29
影响因子：
4.4
通讯作者：
Chen, Lin X.
中科院分区：
文献类型：
--
作者：
Hsu, Darren J.;Leshchev, Denis;Chen, Lin X.
在过去的几十年里，分子动力学(MD)方法的发展有助于预测天然构象以外的大分子结构，目的是探索蛋白质的能量格局。然而，计算结构并不总是与实验观测结果一致，这要求进一步发展分子动力学策略，使计算和实验更紧密地联系在一起。在这里，我们报告了一种可扩展的、高效的MD模拟方法，该方法结合了X射线溶液散射信号作为构象搜索的驱动力，以在天然盆地之外寻找稳定的结构构型。我们进一步证明了包含水化层效应的重要性，以精确描述涉及溶剂暴露区域的大变化的过程，如展开。利用图形处理单元，即使对于大的生物分子，也允许对运行中的散射图案进行高效的全原子计算，从而加速了相关驱动力的计算。在赖氨酸、精氨酸、鸟氨酸结合蛋白的结构转变和十氯丙氨酸的折叠两个模型蛋白质系统上验证了该方法的实用性。我们讨论了本方法将如何帮助解释蛋白质折叠和结合的动态散射实验。
In the past few decades, prediction of macromolecular structures beyond the native conformation has been aided by the development of molecular dynamics (MD) protocols aimed at exploration of the energetic landscape of proteins. Yet, the computed structures do not always agree with experimental observables, calling for further development of the MD strategies to bring the computations and experiments closer together. Here, we report a scalable, efficient MD simulation approach that incorporates an x-ray solution scattering signal as a driving force for the conformational search of stable structural configurations outside of the native basin. We further demonstrate the importance of inclusion of the hydration layer effect for a precise description of the processes involving large changes in the solvent exposed area, such as unfolding. Utilization of the graphics processing unit allows for an efficient all-atom calculation of scattering patterns on-the-fly, even for large biomolecules, resulting in a speed-up of the calculation of the associated driving force. The utility of the methodology is demonstrated on two model protein systems, the structural transition of lysine-, arginine-, ornithine-binding protein and the folding of deca-alanine. We discuss how the present approach will aid in the interpretation of dynamical scattering experiments on protein folding and association.