Advances over the past decade have made it possible to extract elastic constants of lipid assemblies from molecular dynamics simulations. We summarize existing strategies for obtaining membrane elastic moduli and clarify the differences in the underlying approaches. We analyze these strategies in depth, including several important advantages and limitations. By addressing these limitations, we obtain a newly formulated spatially local methodology for extracting bending and tilt moduli: The Real Space Instantaneous Surface Method (ReSIS). With its freely available implementation, this method is designed for highly dynamic systems with arbitrary interface geometries. We demonstrate how the method provides consistent results for membranes of arbitrary size. In addition, we describe alternative implementations of various Fourier-space methods, and use these to compare the results from the different available methods and from published computational data. We specifically focus on the tilt modulus, where very large differences between Fourier and real-space based methods are observed, including those derived using ReSIS. These discrepancies are likely due to the known difference between model moduli and thermodynamic moduli that are derived from the corresponding response functions. In addition, we reexamine the issue of angular degeneracy and its effect on conformational ensembles. Finally, a van ’t Hoff analysis of the tilt and bending moduli reveals that both modes act as entropic springs and that enthalpy favors nonzero tilt, perhaps heralding the spontaneous lipid chain tilt of the gel phase at lower temperatures.

过去十年的进步使得从分子动力学模拟中提取脂质组装体的弹性常数成为可能。我们总结了获得膜弹性模量的现有策略，并阐明了基本方法之间的差异。我们对这些策略进行了深入分析，包括几个重要的优点和局限性。通过解决这些限制，我们获得了一种新制定的空间局部方法来提取弯曲和倾斜模量：实空间瞬时表面法（ReSIS）。凭借其免费提供的实现，该方法适用于具有任意接口几何形状的高动态系统。我们演示了该方法如何为任意大小的膜提供一致的结果。另外，我们描述了各种傅立叶空间方法的替代实现，并使用它们来比较不同可用方法和已发布的计算数据的结果。我们特别关注于倾斜模量，其中观察到傅立叶方法与基于实空间的方法之间的差异非常大，包括那些使用ReSIS推导的方法。这些差异可能是由于模型模量和热力学模量之间的已知差异所致，这些差异是从相应的响应函数得出的。此外，我们重新检查角度退化的问题及其对构象合奏的影响。最后，对倾斜模量和弯曲模量的van't Hoff分析表明，两种模式都起着熵弹簧的作用，而焓则倾向于非零倾斜，这也许预示着低温下凝胶相的自发脂质链倾斜。