MOLECULAR DYNAMICS SIMULATIONS OF SITE-SPECIFIC PROTEI-DNA INTERACTIONS

位点特异性蛋白质-DNA 相互作用的分子动力学模拟

• 批准号: 8171838
• 负责人: LINDA JEN-JACOBSON
• 金额: $ 0.11万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171838
• 关键词: Address; Award; Benchmarking; Code; Complex; Computer Retrieval of Information on Scientific Projects Database; Computer Simulation; Computer software; Crystallography; DNA; DNA Restriction Enzymes; Data; Deoxyribonuclease EcoRI; Development; Funding; Future; Grant; Institution; Investigation; Proteus; Publishing; Research; Research Personnel; Resource Allocation; Resources; Role; Running; Scientist; Services; Site; Source; Specificity; Structure; System; Time; United States National Institutes of Health; Writing; base; improved; interest; molecular dynamics; mutant; novel; simulation; supercomputer

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We were awarded service units on the TCS in the form of a Medium Resource Allocation grant to address hypotheses regarding the role of dynamics in restriction endonuclease specificity. One of the aims of this grant was to use computational simulations to study the interactions of a promiscuous mutant EcoRI endonuclease with its DNA recognition site. We used molecular dynamics (MD) simulations to ask if simulations could reproduce the relatively subtle differences between mutant and wild-type complexes that were observed by x-ray crystallography. Indeed, the MD trajectories confirm many of the features observed in the experimental structures. The computational data also point to some novel differences between the two complexes that warrant further investigation by conducting simulations of significantly increased duration. When we applied for service units, we based the amount of our request on published benchmarks for a system with size similar to ours, running the pmemd code (Amber8 software suite) on the TCS. These benchmarks do not include the time required for file i/o which represents a significant barrier to efficient scaling when writing to disc volumes on the TCS. Thus our MRAC allocation will run out before we are able to address some of the interesting questions prompted by our simulations. We engaged in extended discussions with PSC scientists Troy Wymore and Shawn Brown who strongly recommended investigating the possibility that running simulations of our systems on the Cray XT3 will improve both scaling and throughput. We would therefore like to request a development allocation of service units on the XT3 as a means to extend the duration of our current simulations as well as to explore the capabilities of this new PSC resource to make more efficient use of future supercomputer time.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 我们以中等资源分配拨款的形式获得了TCS上的服务单位，以解决关于动力学在限制性内切酶特异性中的作用的假说。这项资助的目的之一是使用计算模拟来研究混杂突变的EcoRI内切酶与其DNA识别位点的相互作用。我们使用分子动力学(MD)模拟来询问模拟是否能再现X射线结晶学观察到的突变型和野生型复合体之间相对细微的差异。事实上，MD轨迹证实了在实验结构中观察到的许多特征。计算数据还指出了两个复合体之间的一些新的差异，这些差异值得通过进行持续时间显著增加的模拟来进一步研究。当我们申请服务单位时，我们的请求量是基于发布的基准，该系统具有与我们类似的规模，在TCS上运行pmend代码(Amber8软件套件)。这些基准不包括文件I/O所需的时间，当写入到TCS上的盘卷时，文件I/O表示有效扩展的显著障碍。因此，我们的MRAC分配将在我们能够解决我们的模拟所引发的一些有趣的问题之前用完。我们与PSC科学家Troy Wymore和Shawn Brown进行了广泛的讨论，他们强烈建议调查在Cray XT3上运行我们的系统模拟将提高可伸缩性和吞吐量的可能性。因此，我们希望对XT3上的服务单元进行开发分配，以延长我们当前模拟的持续时间，并探索这一新的PSC资源的能力，以更有效地利用未来的超级计算机时间。