Department of Supramolecular Biology, Graduate School of Nanobioscience, Yokohama City University, 1-7-29 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
J Chem Phys. 2011 Jan 14;134(2):025102. doi: 10.1063/1.3526488.
The combination of small-angle X-ray solution scattering (SAXS) experiments and molecular dynamics (MD) simulations is now becoming a powerful tool to study protein conformations in solution at an atomic resolution. In this study, we investigated effects of ionic strength on SAXS data theoretically by using MD simulations of hen egg white lysozyme at various NaCl concentrations from 0 to 1 M. The calculated SAXS excess intensities showed a significant dependence on ion concentration, which originates from the different solvent density distributions in the presence and absence of ions. The addition of ions induced a slow convergence of the SAXS data, and a ∼20 ns simulation is required to obtain convergence of the SAXS data with the presence of ions whereas only a 0.2 ns simulation is sufficient in the absence of ions. To circumvent the problem of the slow convergence in the presence of ions, we developed a novel method that reproduces the SAXS excess intensities with the presence of ions from short MD trajectories in pure water. By applying this method to SAXS data for the open and closed forms of transferrin at 1 M ion concentration, the correct form could be identified by simply using short MD simulations of the protein in pure water for 0.2 ns.
小角 X 射线散射（SAXS）实验与分子动力学（MD）模拟的结合，如今已成为研究溶液中蛋白质构象的强大工具，可达到原子分辨率。本研究通过对不同 NaCl 浓度（0 至 1 M）下鸡卵清溶菌酶的 MD 模拟，从理论上研究了离子强度对 SAXS 数据的影响。计算出的 SAXS 过剩强度与离子浓度有显著的依赖关系，这源于存在和不存在离子时溶剂密度分布的不同。离子的加入导致 SAXS 数据的收敛速度变慢，在存在离子的情况下需要进行约 20 ns 的模拟才能使 SAXS 数据收敛，而在不存在离子的情况下仅需 0.2 ns 的模拟。为了避免离子存在时收敛速度变慢的问题，我们开发了一种新方法，可以从纯水中的短 MD 轨迹中重现存在离子时的 SAXS 过剩强度。通过将该方法应用于 1 M 离子浓度下转铁蛋白的开放和闭合形式的 SAXS 数据，仅使用纯水中蛋白质的 0.2 ns 短 MD 模拟，就可以正确识别出蛋白质的构象。
