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。次级项目的主要支助 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 安东的计算机时间分配要求调查非常重要的方法和采样的限制与分子动力学（MD）模拟的DNA和蛋白质-DNA复合物的结构和动力学。 这些问题的严重性很可能只有采取多团体、“分而治之”的办法才能得到最彻底的解决。 该提案是代表ABC联盟提交的，ABC联盟是一个由高级研究人员领导的国际组织，他们在各种理论和应用背景下对核酸的MD具有相当丰富的经验。 该联盟的美国成员将在Anton上进行模拟，结果将与ABC联盟的其他成员分享，以进行分析，考虑结果的功能影响，并准备出版物。 我们提出的研究的主要目标是利用~10微秒（？s）MD模拟以充分表征a）DNA的热可及亚态的结构和动力学、关键动力学量的弛豫时间和动力学结构的收敛性质以及与其它分子（盐、水等）的相互作用和B）在全原子、全溶剂MD应用于蛋白质DNA复合物的研究中将遇到的相应问题。 在以前发表的文章中提供了对每个系统的初步研究，从不同的参与者，和工具，构象和螺旋分析，主成分分析，并通过关系数据库的共享和分配结果的方法。

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.