Developing computational methods to determine the thermodynamics of lipid phase coexistence

项目说明 近年来，人们对相分离的作用有了新的认识 生物学，特别是脂膜中的相共存，定义了 我们细胞内部和周围的边界。对这一现象的研究 由于时间和时间的原因，分子模拟方法仍然具有挑战性 涉及长度尺度，虽然粗粒度的模拟已经复制了 相共存的存在，到目前为止还没有确定的方法 支配这一过程的热力学。 我们将开发一种新的方法来填补这一空白，围绕着加权 使用基于接触的集体变量的集合模拟技术。我们会 实施并测试用于测量自由能的协议，以将3- 组件膜，使用粗粒模拟与马提尼 力场作为我们的测试套件。此外，我们还将实现并验证新的 一种将加权集成与温度副本交换相结合的方法 进一步加快计算的统计收敛的方法。最后，我们会 扩展方法以处理表面绑定的划分和聚合 共存相间的多肽，以抗真菌脂肽风云素为 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.