PROTEIN FOLDING DYNAMICS IN TORSIONAL ANGLE SPACE

扭转角空间中的蛋白质折叠动力学

• 批准号: 6282167
• 负责人: HAROLD A. SCHERAGA
• 金额: $ 4.25万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-12-01 至 1998-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6282167
• 关键词: biological products; biomedical resource; computers; proteins; structural biology; technology /technique

A Brownian dynamics treatment in torsional angle space was constructed for the simulation of conformational dynamics of macromolecules with fixed bond lengths and bond angles and with an arbitrary intramolecular potential energy function. The advantages of the torsional angle space treatment over similar treatments (Brownian dynamics or molecular dynamics) in atomic coordinate space are that the number of variables is reduced by roughly a factor of 10 and that the integration time step size is increased by three to four orders of magnitude. Consequently, the exploration of global conformational relaxation processes becomes computationally possible. The treatment is a general purpose one applicable to all macromolecular conformational relaxation processes (e.g., protein folding kinetics, drug/ligand docking on to target proteins, conformational multiple-minima problems, etc.). The torsional angle space Brownian dynamics treatment has been used to study the mechanism and kinetics of protein folding by using continuum rigid chain molecules (with unit bond lengths and tetrahedral bond angles). It is found that the torsional angle space approach is much faster and more reliable than similar approaches in atomic coordinate space. The simulation results also suggest that the short-ranged Lennard-Jones binary interactions alone are not sufficient to fold the chain molecules, and that hydrophobic collapse is essential for the folding processes. In our simplified protein folding model, the hydrophobic collapse is achieved by introducing global dipole interactions. The collapse of the chain molecule induced by dipole interactions significantly reduces the folding time. The chain collapse processes effectively bring the atoms into the (short) range of Lennard-Jones attractions, which then, in turn, are able to play their role in the folding processes; without such collapse the folding processes are highly frustrated.

扭转角度的布朗动力处理是 用于模拟构象动力学的构建 具有固定键长和键角的大分子，以及 任意分子内势能函数。 优势 相似处理的扭转角空间处理（布朗尼 原子坐标空间中的动力学或分子动力学）是 变量的数量减少了大约10倍，并且 集成时间步长增加了三到四个阶 震级。 因此，探索全球构象 放松过程在计算上成为可能。 治疗 是适用于所有大分子的通用物 构象松弛过程（例如，蛋白质折叠动力学， 药物/配体靶向蛋白质，构象 多个米尼马问题等）。扭转角度空间布朗尼 动力处理已用于研究机制和动力学 通过使用连续刚性链分子（用单位）折叠蛋白质的折叠 键长和四面体键角）。 发现 扭转角度空间方法比 原子坐标空间中的类似方法。 仿真结果 还建议短距离Lennard-Jones二进制互动 一个人不足以折叠链分子，并且 疏水性崩溃对于折叠过程至关重要。 在我们的 简化的蛋白质折叠模型，实现了疏水性崩溃 通过引入全局偶极相互作用。 链的崩溃 偶极相互作用诱导的分子显着降低了 折叠时间。 链倒塌过程有效地带来了 原子进入（短）Lennard-Jones景点，然后， 反过来，能够在折叠过程中发挥作用。没有 这样的折叠过程非常沮丧。