LES--NEW METHOD FOR COMPUTER SIMULATIONS OF PROTEINS

这项研究旨在进一步开发一种新计算机的能力 仿真技术，大大提高了范围和通用性 普通分子动力学模拟。三大方向将是 探索： (i)小肽的结构测定。 肽的结构 (when存在）具有重大意义。多肽转移 信号的受体和调查他们的构象可能会导致 替代品的设计。此外，短肽的结构可以 提示蛋白质折叠过程的起始位点。存在 具有高概率的独特结构的肽段可以 大大加快了折叠过程。 (ii)低分辨率蛋白质结构的精细化。 当今 基于统计的计算方法的能力 方法稳步增加。然而，到目前为止， 获得的分辨率较低。"低分辨率"全局 搜索方法和原子细节细化程序的基础上LES是一个 有前途的方法。 (iii)分子动力学时间尺度的扩展。 LES提供 对分子事件进行采样的统计数据要多得多。动力学 LES是平均场近似。然而，在双星碰撞的情况下， 修正我们开发的LES描述扩散定量和 将被用来研究配体逃逸的蛋白质基质上的数十个 纳秒的时间尺度，一个时间尺度， 分子动力学之前。

This research aims to further develop the capabilities of a new computer simulation technique that significantly enhances the scope and versatility of usual molecular dynamics simulations. Three general directions will be explored: (i) Determination of structure of small peptides. Structure of peptides (when existent) are of significant interest. Many peptides transfer signals to receptors and investigation of their conformations may lead to the design of substitutes. Furthermore, structure of short peptides may suggest initiation site for the process of protein folding. Presence of peptide segments with high probability for a unique structure may accelerate considerably the folding process. (ii) Refinement of low resolution protein structure. Nowadays the capabilities of computational methods that are based on statistical approaches are steadily increased. Nevertheless, so far the structure obtained are of low resolution. The combination of "low resolution" global search methods and atomic detail refinement procedures based on LES is a promising approach. (iii) Extension of molecular dynamics time scales. The LES provides considerably more statistics for sampling molecular events. For dynamics LES is a mean field approximation. However, with a binary collision correction developed by us the LES describes diffusion quantitatively and will be employed to study ligand escapes from a protein matrix on the tens of nanoseconds time scale, a time scale that was not accessible to molecular dynamics before.