Wang Yukun, Zhao Tangzheng, Wei Dongqing, Strandberg Erik, Ulrich Anne S, Ulmschneider Jakob P
The State Key Laboratory of Microbial Metabolism and College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
The State Key Laboratory of Microbial Metabolism and College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China; College of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
Biochim Biophys Acta. 2014 Sep;1838(9):2280-8. doi: 10.1016/j.bbamem.2014.04.009. Epub 2014 Apr 18.
Membrane-active antimicrobial peptides (AMPs) are challenging to study experimentally, but relatively easy to investigate using molecular dynamics (MD) computer simulations. For this reason, a large number of MD studies of AMPs have been reported over recent years. Yet relatively little effort has focused on the validity of such simulations. Are these results reliable, and do they agree with what is known experimentally? And how much meaningful information can be obtained? To answer these questions, we demonstrate here some of the requirements and limitations of running MD simulations for several common AMPs: PGLa, melittin, maculatin and BP100. The two most important findings are: (a) simulation results depend strongly on force field parameters, making experimental verification of the simulations obligatory, and (b) slow orientational and conformational fluctuations mean that much longer sampling timescales (multi-μs) are needed if quantitative agreement between simulation averages and experimental data is to be achieved. This article is part of a Special Issue entitled: Interfacially Active Peptides and Proteins. Guest Editors: William C. Wimley and Kalina Hristova.
膜活性抗菌肽（AMPs）的实验研究颇具挑战性，但利用分子动力学（MD）计算机模拟进行研究则相对容易。因此，近年来已有大量关于AMPs的MD研究报告。然而，相对较少的精力集中在这类模拟的有效性上。这些结果可靠吗？它们与实验所知的情况相符吗？又能获得多少有意义的信息呢？为了回答这些问题，我们在此展示了对几种常见AMPs（PGLa、蜂毒肽、maculatin和BP100）进行MD模拟的一些要求和局限性。两个最重要的发现是：（a）模拟结果强烈依赖于力场参数，这使得对模拟进行实验验证成为必要；（b）缓慢的取向和构象波动意味着，如果要实现模拟平均值与实验数据之间的定量一致性，则需要长得多的采样时间尺度（数微秒）。本文是名为：界面活性肽和蛋白质的特刊的一部分。客座编辑：William C. Wimley和Kalina Hristova。
