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首页> 外文学位 >Computational investigations of biomolecular conformational transitions: Ligand binding, transition pathways and key residues.
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Computational investigations of biomolecular conformational transitions: Ligand binding, transition pathways and key residues.

机译：生物分子构象转变的计算研究：配体结合，转变途径和关键残基。

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摘要

Conformational transitions (i.e. structural changes) are an integral part of the functional cycle of many biomolecules and act as an important regulatory mechanism to keep cells functioning normally. There are a few interesting mechanistic questions for conformational transitions in general including the molecular mechanism of ligand binding, the dominant transition pathways and associated energetics and kinetics, and the key residues important for conformational transitions.;This dissertation aims to address these mechanistic questions with representative systems and problems using computational and simulation approaches. Specifically, in the aspect of ligand binding, the mechanism of non-covalent binding of salt ions and small solutes to peptides is investigated at the molecular level. Furthermore, the coupling behavior between DNA binding and disruption and formation of salt bridges in integration host factor (IHF) is also studied. As for dominant transition pathways, the activation mechanism (pathways) of a signaling protein CheY is explored at the atomic resolution with a synergistic combination of transition path sampling and free energy simulations. With the long-term goal of studying transition pathways for mechano-biological conformational transitions in general, a coarse grained computational framework combining continuum mechanics and continuum electrostatics is also developed. Moreover, to facilitate comparisons with experiments, the theoretical procedures for kinetic calculations of conformational transitions (the ion/solute conduction in particular) are also derived. Finally, the exploration of key residues for conformational transitions is discussed with the myosin motor domain as the model system.
机译：构象转变（即结构改变）是许多生物分子功能周期的组成部分，并且是保持细胞正常功能的重要调节机制。一般而言，构象转变存在一些有趣的力学问题，包括配体结合的分子机理，主要的转变途径和相关的能级和动力学，以及对于构象转变重要的关键残基。系统和使用计算和仿真方法的问题。具体地，在配体结合方面，在分子水平上研究了盐离子和小溶质与肽的非共价结合机理。此外，还研究了DNA结合与整合宿主因子（IHF）中盐桥的破坏和形成之间的偶联行为。至于主要的过渡途径，信号蛋白CheY的激活机制（途径）是在原子分辨率下通过过渡途径采样和自由能模拟的协同组合而探索的。出于长期研究机械-生物构象转变的转变路径的长期目标，还开发了一种将连续力学和连续静电相结合的粗粒度计算框架。此外，为了便于与实验进行比较，还导出了构象转变（特别是离子/溶质传导）动力学计算的理论程序。最后，以肌球蛋白运动域为模型系统讨论了构象转变关键残基的探索。

著录项

  • 作者

    Ma, Liang.;

  • 作者单位

    The University of Wisconsin - Madison.;

  • 授予单位 The University of Wisconsin - Madison.;
  • 学科 Biophysics General.
  • 学位 Ph.D.
  • 年度 2009
  • 页码 215 p.
  • 总页数 215
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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