Pfeiffer S, Fushman D, Cowburn D
Laboratory of Physical Biochemistry, The Rockefeller University, New York, New York 10021-6399, USA.
Proteins. 1999 May 1;35(2):206-17.
A nonzero net charge of proteins at pH 7 is usually compensated by the addition of charge-balancing counter ions during molecular dynamics simulation, which reduces electrostatic interactions. For highly charged proteins, like the betaARK1 PH domain used here, it seems reasonable to also add explicit salt ions. To assess the impact of explicit salt ions, two molecular dynamics simulations of solvated betaARK1 PH domain have been carried out with different numbers of Cl- and Na+ ions, based on the Cornell et al. force field and the Ewald summation, which was used in the treatment of long-range electrostatic interactions. Initial positions of ions were obtained from the AMBER CION program. Increasing the number of ions alters the average structure in loop regions, as well as the fluctuation amplitudes of dihedral angles. We found unnaturally strong interactions between side chains in the absence of salt ions. The presence of salt ions reduces these electrostatic interactions. The time needed for the equilibration of the ionic environment around the protein, after initial placement of ions close to oppositely charged side chains, is in the nanosecond time range, which can be shortened by using a higher ionic strength. Our results also suggest selecting those methods that do not place the ions initially close to the protein surface.
在pH 7时蛋白质的非零净电荷通常在分子动力学模拟过程中通过添加电荷平衡抗衡离子来补偿，这会减少静电相互作用。对于像此处使用的βARK1 PH结构域这样的高电荷蛋白质，添加明确的盐离子似乎也是合理的。为了评估明确盐离子的影响，基于康奈尔等人的力场和用于处理长程静电相互作用的埃瓦尔德求和法，对溶剂化的βARK1 PH结构域进行了两次分子动力学模拟，其中Cl-和Na+离子的数量不同。离子的初始位置从AMBER CION程序获得。增加离子数量会改变环区域的平均结构以及二面角的波动幅度。我们发现在没有盐离子的情况下侧链之间存在异常强的相互作用。盐离子的存在会减少这些静电相互作用。在最初将离子放置在带相反电荷的侧链附近后，蛋白质周围离子环境达到平衡所需的时间在纳秒范围内，通过使用更高的离子强度可以缩短该时间。我们的结果还表明应选择那些最初不将离子放置在蛋白质表面附近的方法。
