Chemical, Biological and Radiological Sciences, Defence Science and Technology Laboratory , Porton Down, Salisbury, Wiltshire SP4 0JQ, U.K.
Chemistry, University of Southampton , Highfield, Southampton SO17 1BJ, U.K.
J Chem Theory Comput. 2017 Nov 14;13(11):5683-5696. doi: 10.1021/acs.jctc.7b00643. Epub 2017 Oct 16.
For molecular dynamics simulations of biological membrane systems to live up to the potential of providing accurate atomic level detail into membrane properties and functions, it is essential that the force fields used to model such systems are as accurate as possible. One membrane property that is often used to assess force field accuracy is the carbon-hydrogen (or carbon-deuterium) order parameters of the lipid tails, which can be accurately measured using experimental NMR techniques. There are a variety of analysis tools available to calculate these order parameters from simulations and it is essential that these computational tools work correctly to ensure the accurate assessment of the simulation force fields. In this work we compare many of these computational tools for calculating the order parameters of POPC membranes. While tools that work on all-atom systems and tools that work on saturated lipid tails in general work extremely well, we demonstrate that the majority of the tested tools that calculate the order parameters for unsaturated united-atom lipid tails do so incorrectly. We identify tools that do perform accurate calculations and include one such program with this work, enabling rapid and accurate calculation of united-atom lipid order parameters. Furthermore, we discuss cases in which it is nontrivial to appropriately predict the unsaturated carbon order parameters in united-atom systems. Finally, we examine order parameter splitting for carbon 2 in sn-2 lipid chains, demonstrating substantial deviations from experimental values in several all-atom and united-atom lipid force fields.
为了使生物膜系统的分子动力学模拟充分发挥潜力，提供对膜性质和功能的准确原子水平细节，用于模拟此类系统的力场尽可能准确是至关重要的。经常用于评估力场准确性的膜性质之一是脂质尾部的碳-氢（或碳-氘）序参数，该参数可以使用实验 NMR 技术准确测量。有各种分析工具可用于从模拟中计算这些序参数，并且必须确保这些计算工具正确运行，以确保对模拟力场的准确评估。在这项工作中，我们比较了许多用于计算 POPC 膜序参数的计算工具。虽然适用于全原子系统的工具和适用于饱和脂质尾部的工具通常效果非常好，但我们证明了大多数用于计算不饱和联合原子脂质尾部序参数的测试工具的计算结果不正确。我们确定了执行准确计算的工具，并在这项工作中包含了一个这样的程序，从而能够快速准确地计算联合原子脂质序参数。此外，我们讨论了在联合原子系统中适当地预测不饱和碳序参数并不简单的情况。最后，我们检查了 sn-2 脂质链中碳 2 的序参数拆分，在几种全原子和联合原子脂质力场中都显示出与实验值的实质性偏差。
