A New Method for Biomembrane Simulations

该项目涉及一种新的计算方法，旨在解决复杂生物分子系统计算机模拟中的一个基本挑战：多个空间和时间尺度之间的接口和反馈。生物分子系统可以具有从微观(纳秒)到宏观(毫秒到小时)的时间尺度上发生的动力学，以及从埃到毫米甚至更远的长度尺度上的动力学。该项目的具体目标将是模拟脂质双层(细胞膜)中的这种过程。因此，重点将放在开发和应用新的模拟技术，以探索生物膜对外部扰动(如机械应力、pH梯度、渗透力等)的非线性响应。这项研究将利用集成的计算机模拟能力，将微观、原子水平的模拟信息与宏观、连续水平的模拟联系起来。从最广泛的背景来看，这个跨学科的项目代表着朝着最终模拟生物体的关键组成部分迈出了一步，从原子模拟信息开始。在短期内，模拟细胞膜对各种环境扰动的反应的能力开辟了一条途径，以设计在其他环境中调节细胞膜性质的试剂；例如，增加/降低对裂解的敏感性，调节特定双层的通透性以增加药物传输，并帮助设计用于药物输送目的的新型脂质体。

This project involves a new computational methodology developed to address a fundamental challenge in the computer simulation of complex biomolecular systems: the interfacing and feedback between multiple spatial and temporal scales. Biomolecular systems can possess dynamics that occur on time scales ranging from the microscopic (nanoseconds) to the macroscopic (milliseconds to hours), and on length scales from Angstroms to millimeters and beyond. The specific goal of the project will be to simulate such processes in lipid bilayers (cell membranes). The focus will therefore be on the development and application of the new simulation technology to explore the nonlinear response of biomembranes to external perturbations such as mechanical stresses, pH gradients, osmotic forces, etc. The research will utilize an integrated computer simulation capability to link the microscopic, atomic level simulation information with macro-scale, continuum-level modeling. Viewed in its broadest context, this interdisciplinary project represents a step toward the eventual simulation of the key components of living organisms beginning with atomistic simulation information at its foundation. In the shorter term, the capability to model the response of a cell membrane to various environmental perturbations opens a pathway to design agents to modulate the properties of cell membranes in other contexts; for example, to increase/decrease susceptibility to lysis, to modulate permeability of specific bilayers in order to increase drug transport and to help design novel liposomes for drug delivery purposes.