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Simulation of Multi-Protein systems

多蛋白系统的模拟

基本信息

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
项目类别：
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&apos 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

项目摘要

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.

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。