Simulation of Multi-Protein systems

多蛋白系统的模拟

• 批准号: 10680446
• 负责人: Dmytro Kozakov
• 金额: $ 31.08万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-20 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10680446
• 关键词: 3-Dimensional; Agreement; Algorithms; Alzheimer' s disease model; Aprotinin; Area; Award; Binding; Biological Models; Biological Products; Bovine Serum Albumin; Capsid; Cell physiology; Cells; Cellular biology; Collaborations; Complex; Crowding; Data; Development; Disease; Erythrocytes; Evaluable Disease; Evaluation; Formulation; Fourier Transform; Goals; Grant; Hemoglobin; Image Compression; Liquid substance; Mass Spectrum Analysis; Memory; Methods; Minor; Modeling; Molecular Conformation; Multiprotein Complexes; Mycoplasma genitalium; National Institute of General Medical Sciences; Nucleosome Core Particle; Pathway interactions; Peptides; Performance; Pharmaceutical Preparations; Property; Protein Conformation; Proteins; Resolution; Rest; Sampling; Speed; Structure; Sum; System; Validation; Variant; Writing; experimental group; experimental study; flexibility; gamma-Crystallins; improved; innovation; insight; method development; molecular assembly/self assembly; molecular modeling; mouse model; multicatalytic endopeptidase complex; novel strategies; particle; protein aggregation; self assembly; simulation; therapeutic development

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.

具有原子细节的大型多组分分子组装体的模拟非常重要 朝着理解细胞过程迈出了一步。该提案的目标是开发一个 模拟由多个副本组成的多蛋白质系统的有效方法 蛋白质的类型，每种都有许多离散的构象。我们的方法的基础是 观察两个蛋白质（或离散蛋白质构象）之间的相互作用能 在一个系综内）——可以在整个旋转平移空间上有效地计算 使用快速流形傅里叶变换（FMFT）相关方法。给定任何构象 对于复杂的多粒子系统，其能量可以通过两两求和来轻松获得 从查找表中提取的相互作用能量。高效的关键创新 实现这个方法是我们压缩和存储相互作用能量查找表的能力 使用小波集在内存中。我们将在两个应用程序中应用该方法。第一个是 多蛋白质组装及其关联途径的模拟，可能结合 具有低分辨率质谱 (MS) 和 EM 数据，提供机械洞察 细胞功能。第二个是模拟蛋白质聚集和拥挤，即 对于细胞生物学和治疗开发的基本理解非常重要。