Development of Generalized-Ensemble Algorithms and their Application in Protein Studies

广义集成算法的发展及其在蛋白质研究中的应用

• 批准号: 1266256
• 负责人: Ulrich Hansmann
• 金额: $ 41万
• 依托单位: University of Oklahoma Norman Campus
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1266256&HistoricalAwards=false
• 关键词: Development; Generalized; Ensemble; Algorithms; their

Ulrich Hansmann of the University of Oklahoma is supported by the Chemical Theory, Models and Computational Methods program in the Chemistry Division to develop theoretical and computational approaches aimed at overcoming limitations of generalized-ensemble and replica-exchange techniques in protein folding studies. For this purpose, the replica exchange protocol is reformulated to enable its efficient use in multiscale and explicit solvent simulations; and an automatic procedure is established for designing ensembles that maximize the sampling of folding/unfolding transitions. These techniques are then used to explore the utility of a multi-funnel concept for describing the role of mutations, changes in environment, or interaction with other molecules on protein folding. For this purpose, mutation-induced changes in the folding landscape of the A and B domain of protein G and the inter-conversion between the two functional forms of lymphotactin are studied. The project aims at overcoming sampling difficulties that hold back the use of atomistic molecular dynamics or Monte Carlo simulations for complementing experiments in exploring the molecular machinery of cells. New techniques are developed and applied to study the folding mechanism of especially interesting proteins, in order to obtain a more complete view of protein folding and cellular processes. In order to broaden the impact of the project an annual workshop "From Computational Biophysics to Systems Biology" is organized; and summer internships are offered to undergraduate students from diverse backgrounds.

俄克拉荷马州大学的Ulrich Hansmann得到了化学系化学理论、模型和计算方法项目的支持，开发了旨在克服广义系综和复制交换技术在蛋白质折叠研究中的局限性的理论和计算方法。 为了这个目的，副本交换协议重新制定，使其有效地使用多尺度和明确的溶剂模拟，并建立一个自动程序设计合奏，最大限度地提高折叠/展开过渡的采样。然后，这些技术被用来探索多漏斗概念的效用，用于描述突变，环境变化或与其他分子的相互作用对蛋白质折叠的作用。为此目的，突变诱导的变化的折叠景观的A和B结构域的蛋白G和之间的相互转换的两种功能性形式的荧光蛋白进行了研究。该项目旨在克服取样困难，这些困难阻碍了原子分子动力学或蒙特卡罗模拟的使用，以补充探索细胞分子机制的实验。新的技术被开发和应用于研究特别感兴趣的蛋白质的折叠机制，以获得蛋白质折叠和细胞过程的更完整的视图。为了扩大该项目的影响，组织了一次年度讲习班“从计算生物物理学到系统生物学”;并为来自不同背景的本科生提供暑期实习机会。