MOLECULAR DYNAMICS OF DNA AND PROTEIN DNA COMPLEXES: A PROPOSAL FOR OBTAINING M

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 为了用分子动力学(MD)模拟DNA和蛋白质-DNA复合体的结构和动力学，需要在ANTON上分配计算机时间来调查非常重要的方法学和采样限制。这些问题的严重性可能只有通过多个群体的“分而治之”的方法才能得到最彻底的解决。本提案是代表ABC联盟提交的，该联盟是一个由资深调查人员领导的国际组织，在各种理论和应用背景下对核酸的MD有相当的经验。模拟将由总部设在美国的联盟成员对Anton进行，结果将与ABC联盟的其他成员共享，用于分析、考虑结果的功能影响和准备出版物。我们所提出的研究的主要目标是利用~10微秒(S)分子动力学模拟来充分表征a)DNA热可及态的结构和动力学，关键动力学参数的驰豫时间和动力学结构的收敛性质，以及与其他分子(盐、水等)的相互作用，以及b)在应用全原子、全溶剂分子动力学研究蛋白质DNA络合物时将遇到的相应问题。不同参与者以前发表的文章提供了对选定进行研究的每个系统的初步研究，并提供了用于构象和螺旋分析、主成分分析以及通过关系数据库共享和分发结果的方法的工具。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. An allocation of computer time on Anton is requested to investigate very significant methodological and sampling limitations with molecular dynamics (MD) simulations of the structure and dynamics of DNA and protein-DNA complexes. The issues are of a magnitude that is likely only and most thoroughly addressed with a multi-group, "divide and conquer" approach. This proposal is submitted on behalf of the ABC consortium, an international group led by senior investigators with considerable experience with MD on nucleic acids in various theoretical and applied contexts. The simulations will be performed on Anton by the USA-based members of the consortium, and the results will be shared with others in the ABC Consortium for analysis, consideration of the functional implications of the results, and the preparation of publications. The major objectives of our proposed studies is to utilize ~10 micro-second (?s) MD simulations to fully characterize a) the structure and dynamics of the thermally accessible substates of DNA, the relaxation times of key dynamical quantities and convergence properties of the dynamical structure, and interactions with other molecules (salt, water, etc) and b) the corresponding issues that will be encountered in applications of all-atom, full solvent MD to the study of protein DNA complexes. Preliminary studies on each of the systems selected for study are provided in previously published articles from the various participants, and tools are in place for conformational and helical analyses, principle component analyses, and methods for sharing and distribution of results via relational data bases.