NANOSECOND DYNAMICS OF SHEET PROTEIN COMPARISON & EXPER DATA INTERPRETATION

寡肽和蛋白质的传统处理方法 在分子力学和分子动力学中，假设电荷 对构象变化是不变的。这些费用固定在 开始和在整个模拟过程中保持不变。 尝试使用这些传统方法来解释一些 寡肽构象与pH的实验依赖关系 非常成功。我们的目标集中在特定的方面 折叠过程：它试图理解环境是如何 影响短多肽的构象偏好 序列：AC-ETGTKAELLAKYEATHK-NHMe，反之亦然；即 构象影响可电离基团的pK。在我们的工作中有了新的 提出了解决问题的方法。它明确地考虑了两者之间的耦合 分子的构象和a的电离平衡 给定的pH值。溶剂化自由能和自由能的计算 这个17-残基的电离能(对于它，可用的核磁共振 和CD实验数据表明，这些构象包含一个 在低pH下，右旋α-螺旋片段的能量更高 有利的)使用快速多重网格边界元进行 方法(MBE)。MBE方法被纳入ECEPP/3(经验性 多肽构象能程序)算法计算 分子的电离态与构象的耦合 分子。我们用目前的方法计算的结果 与以前的实验形成鲜明对比的是，与实验结果相当吻合 采用标准技术的应用程序(使用预先分配的费用 每种pH值)。特别是，我们已经能够展示耦合是如何 构象不同导致给定的电离程度不同 残基的类型，例如谷氨酸，在 氨基酸序列，在给定的pH下。这项研究的结果 为讨论稳定的根源提供了可靠的依据。 寡肽构象及其对环境的依赖 条件。我们希望继续发展这一进程。 一系列寡肽的初步探讨和进一步检测 生物兴趣。

The traditional approaches for treating oligopeptides and proteins in molecular mechanics and molecular dynamics assume that the charges are invariant to conformational changes. These charges are fixed at the beginning and are kept constant throughout the whole simulation. Attempts to use these traditional approaches to explain some experimental dependences of oligopeptide conformation on pH have not been very successful. Our goal was focused on a specific aspect of the folding processes: It attempts to understand how the enviroment affects the conformational preference of a short polypeptide with the sequence: Ac-ETGTKAELLAKYEATHK-NHMe, and vice versa; i.e. how the conformation affects the pK's of ionizable groups. In our work a new approach is presented. It considers explicitly the coupling between the conformation of the molecule and the ionization equilibria at a given pH value. Calculations of the solvation free energy and free energy of ionization of this 17-residue (for which the available NMR and CD experimental data indicate that the conformations containing a right-handed alpha-helix segment at low pH are energetically more favorable) were carried out using a fast multigrid boundary element method (MBE). The MBE method was integrated into ECEPP/3 (Empirical Conformational Energy Program for Peptides) algorithm to compute the coupling between the ionization state and the conformation of the molecule. The results of our calculations using the present method agree quite well with experiments, in contrast with previous applications with standard techniques (using pre-assigned charges at each pH). In particular we have been able to show how the coupling to the conformation leads to different degree of ionization of a given type of residue, for example glutamic acid, at different positions in the amino acid sequence, at a given pH. The results of this study provide a sound basis to discuss the origin of the stability of oligopeptide conformations and its dependence on enviromental conditions. We expect to continue with the development of this approach and further testing of a series of oligopeptides of biological interest.