MOLECULAR SIMULATION STUDIES OF BIOLOGICAL MOLECULES

我们在此请求继续支持对 利用分子动力学研究生物大分子的结构和动力学 动力学(MD)和蒙特卡罗(MC)计算机模拟方法。这个 我们的研究重点是开发和健壮的模拟 适用于上述系统的协议，详细说明 对随后的轨迹进行表征并建立 MC方法学应用的可行性、准确性和局限性 这些系统。在此提出的研究将集中在四个方面 领域：a)对现行管理办法的适用性进行关键评估 长度不同的较长DNA寡核苷酸的模拟方案 从大约17-30个碱基对；b)DNA序列的动态结构 在通过弯曲调节生理过程中起重要作用 和/或蛋白质识别和c)结构研究和机制 从复合酶的溶液模拟得出的启示 具有抑制剂/底物和d)蛋白质的MD/MC模拟 参与DNA序列识别，这对 了解基因表达的分子基础。中的重点 我们的项目是详细的结构表征，基于 各种力场，用来仔细检查结果 结晶学、核磁共振和其他可用的实验数据， 识别和分析子状态以及状态的发展 艺术图形分析工具。

We request herein continuation support for the study of the structure and dynamics of biological macromolecules using Molecular Dynamics (MD) and Monte Carlo (MC) computer simulation methods. The focus of our research involves development and robust simulation protocols for application to the above systems, detailed characterization of the ensuing trajectories and establishment of the feasibility, accuracy and limitations of the MC methodology as applied to these systems. The studies proposed herein will focus in four areas: a) critical assessment of the applicability of current M simulation protocols to longer DNA oligonucleotides, varying in length from about 17-30 base pairs; b) dynamical structure of DNA sequences important in the regulation of physiological processes through bending and/or protein recognition and c) structural studies and mechanistic implications derived from solution simulations of an enzyme complexed with an inhibitor/substrate and d) MD/MC simulations of proteins involved in DNA sequence recognition that are significant towards understanding the molecular basis of gene expression. The emphasis in our projects is on detailed structural characterization based on a variety of force fields, scrutinization of the results with crystallographic, NMR and other available experimental data, identifying and analyzing substates and development of state of the art graphical analysis tools.