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。 具体而言，要求计算机时间达到以下目标： (1)我们建议使用分子动力学（MD）模拟来探测 融合肽发挥其功能的机制。 我们有 已经对双层系统进行了MD模拟（见附录B ）包括包含实验井的系统 特征三肽Ala-Phe-Ala。 我们在Ala-Phe-Ala上的工作 系统已经相当成功地再现了订单定位 以及复制这些参数 脂烷基链附近。 鉴于我们有能力很好地模拟 为了有效地表征系统，我们已经开始研究小肽 促进或抑制融合活性。 (2)我们提出 使用平均力模拟的势来获得分子水平的 离子载体缬氨霉素是如何捕获阳离子的。 从这些模拟中，我们将获得关于 能量（自由能，熵和熵）或离子 捕获过程以及详细的结构洞察。 (3)耦合 密度函数/分子力学（DF/MM）方法将用于 研究溶液中反应机理。 我们最近开发了 DF/MM方法在我们实验室内，并已发表初步 使用这个模型。 我们将用DF/MM方法研究质子 水与氢氧根离子发生转移反应， 从分子水平深入了解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， 一种能给出反应分子级细节的技术 在溶液中和未来的酶活性位点中。

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.