Developing computational methods to determine the thermodynamics of lipid phase coexistence

项目描述 近年来，人们对相分离在生物医学中的作用有了新的认识。 生物学，特别是脂质膜中的相共存， 我们细胞内部和周围的界限研究这一现象， 分子模拟方法仍然具有挑战性，因为时间和 涉及的长度尺度，而粗粒度的模拟已经再现 相共存的存在，至今还没有确定的方法 控制这个过程的热力学。 我们将开发一种新的方法，将填补这一空白，围绕加权 系综模拟技术使用基于接触的集体变量。我们将 实施并测试用于测量自由能的方案，以使3- 组件膜，使用MARTINI粗粒度模拟 力场作为我们的测试套件此外，我们将实施和验证一个新的 方法耦合加权系综与温度副本交换，作为一个 进一步加速计算的统计收敛的方法。最后我们将 扩展该方法以处理表面边界的划分和聚合 肽之间的共存相，使用抗真菌脂肽芬枯草菌素作为 一个测试案例

Project Description Recent years have brought a new appreciation for the role of phase separation in biology, and in particular phase coexistence in the lipid membranes that define the boundaries in and around our cells. Studying this phenomenon using molecular simulation methods remains challenging because of the time- and length-scales involved, and while coarse-grained simulations have reproduced the existence of phase coexistence, to date there are no methods for determining the thermodynamics governing the process. We will develop a new method that will fill this gap, built around the weighted ensemble simulation technique using a contact-based collective variable. We will implement and test a protocol for measuring the free energy to demix 3- component membranes, using coarse-grained simulation with the MARTINI force field as our test suite. In addition, we will implement and validate a new method to couple weighted ensemble with temperature replica exchange, as a way to further speed statistical convergence of the calculations. Finally, we will extend the method to handle the partitioning and aggregation of surface-bound peptides between coexisting phases, using the antifungal lipopeptide fengycin as a test case.