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。生物分子系统可以拥有从微观（纳秒）到宏观（毫秒到小时）的时间尺度以及从埃到毫米甚至更远的长度尺度上发生的动力学。该项目的具体目标是模拟脂质双层（细胞膜）中的此类过程。因此，重点将放在新模拟技术的开发和应用上，以探索生物膜对机械应力、pH 梯度、渗透力等外部扰动的非线性响应。该研究将利用集成的计算机模拟功能，将微观、原子级模拟信息与宏观、连续体级建模联系起来。从最广泛的角度来看，这个跨学科项目代表了从原子模拟信息开始最终模拟生物体关键组成部分的一步。从短期来看，模拟细胞膜对各种环境扰动的响应的能力为设计在其他情况下调节细胞膜特性的试剂开辟了一条途径；例如，增加/减少对裂解的敏感性，调节特定双层的渗透性以增加药物转运并帮助设计用于药物递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.