Simulation of Multi-Protein systems

具有原子化细节的大型多组分分子组装的模拟是一个重要的研究方向 向了解细胞过程迈进一步。这项提议的目标是开发一种 多拷贝多蛋白质体系模拟的一种有效方法 蛋白质的几种类型，每一种都有许多离散的构象。我们方法的基础是 观察到两个蛋白质(或离散蛋白质构象)之间的相互作用能 在系综内)-可以在整个转动-平移空间上有效地计算 使用快速流形傅立叶变换(FMFT)相关方法。给出了任何构象 对于复杂的多粒子系统，它的能量可以很容易地通过两两相加得到 从查找表中提取的相互作用能量。高效的关键创新 实现这种方法是我们压缩和存储相互作用能量查找表的能力 在内存中使用小波集。我们将在两个应用中应用该方法。第一个是 多蛋白质组合及其关联途径的模拟，可能是联合 使用低分辨率质谱学(MS)和EM数据，提供对 细胞功能。第二个是蛋白质聚集和拥挤的模拟，这是 对细胞生物学和治疗发展的基本理解很重要。

Simulation of large multi-component molecular assemblies with atomistic details is an important step toward understanding cellular processes. The goal of this proposal is to develop an efficient method for the simulation of multi-protein systems consisting of many copies of a few types of proteins, each in a number of discrete conformations. The basis for our approach is the observation that the interaction energy between two proteins (or discrete protein conformations within an ensemble) – can be efficiently calculated over the entire rotational-translational space using the fast Manifold Fourier transform (FMFT) correlation approach. Given any conformation of a complex multi-particle system, its energy can be easily obtained by summing the pairwise interaction energies extracted from the lookup tables. The key innovation to efficiently implement this method is our ability to compress and store the interaction energy lookup tables in memory using wavelet sets. We will apply the method in two application. The first is simulation of multi-protein assemblies and their association pathways, possibly in conjunction with low resolution Mass Spectrometry (MS) and EM data, providing mechanistic insight into cellular function. The second is simulation of protein aggregation and crowding, which is important for the fundamental understanding of cell biology and therapeutic development.