COMPUTER SIMULATION OF BIOMOLECULAR STRUCTURE, FUNCTION & DYNAMICS

MetaCenter提案旨在了解 生物相关系统的结构、功能和动力学。 具体地说，需要计算机时间才能达到以下目标： (1)我们建议使用分子动力学(MD)模拟来探索 融合多肽执行其功能的机制。我们有 已经对双层系统进行了MD模拟(见附录B )包括一个系统，该系统包含实验结果良好的 表征了三肽Ala-Phe-Ala。我们在Ala-Phe-Ala上的工作 系统在复制订单定位方面相当成功 在双层中的这种多肽，以及再现参数 附近的脂烷基链。鉴于我们能够很好地模拟这一点 我们已经开始了对小肽的研究 促进或抑制融合活性的。(2)我们建议 利用平均力模拟势能获得分子水平 对阳离子如何被离子载体伐林霉素捕获的洞察。 从这些模拟中，我们将获得关于 高能(自由能、热焓和熵)或离子 捕获流程以及详细的结构洞察。(3)耦合 将使用密度泛函/分子力学(DF/MM)方法 研究了溶液中的反应机理。我们最近开发了 我们实验室内的DF/MM方法，并已发表了初步的 使用此模型进行工作。我们将用DF/MM方法研究质子 水与氢氧化物离子的转移反应，得到 从分子水平洞察溶剂如何影响质子转移 反应。总的来说，这些方法代表了令人兴奋的新方法 这项技术将提供关于反应的分子水平的细节 在溶液和未来的酶活性部位。

The MetaCenter proposal is geared towards understanding the structure, function and dynamics of biologically relevant systems. Specifically computer time is requested to reach the following goals: (1) We propose to use molecular dynamics (MD) simulations to probe the mechanism by which fusion peptides carry out their function. We have already carried out MD simulations on bilayer systems ( See Appendix B ) including a system that contains the experimentally well characterized tripeptide Ala-Phe-Ala. Our work on the Ala-Phe-Ala system has been quite successful in reproducing the order positioning of this peptide in the bilayer as well as reproducing the parameters of nearby lipid alkyl chains. Given our ability to model this well characterized system effectively we have begun to study small peptides that either facilitiate or inhibit fusogenic activity. (2) We propose to use potential of mean force simulations to obtain molecular-level insights into how a cation is captured by the ionophore valinomycin. From these simulations we will obtain a detailed picture regarding the energetic ( free energies, enthalpies, and entropies ) or the ion capture process as well as detailed structural insights. (3) Coupled density function/molecular mechanics (DF/MM) methods will be used to study a reaction mechanism in solution. We have recently developed the DF/MM method within our laboratory and have published preliminary work using this model. With the DF/MM method we will study the proton transfer reaction between water and hydroxide ion to obtain molecular-level insights into how solvent affects proton transfer reactions. In general, these methods represent and exciting new technique that will give molecular-level details regarding reactions in solution and in the future enzyme active sites.