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: 7601439
• 负责人: LINDA JEN-JACOBSON
• 金额: $ 0.03万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7601439
• 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; size; 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 我们以中等资源分配补助金的形式获得了 TCS 服务单位，以解决有关动态在限制性内切酶特异性中的作用的假设。这笔资助的目的之一是利用计算模拟来研究混杂突变体 EcoRI 核酸内切酶与其 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可以重现通过 X 射线晶体学观察到的突变型和野生型复合物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种复合体之间的一些新差异，需要通过显着增加持续时间的模拟进行进一步研究。当我们申请服务单位时，我们的请求量基于与我们规模相似的系统的已发布基准，在 TCS 上运行 pmemd 代码（Amber8 软件套件）。这些基准测试不包括文件 I/O 所需的时间，这对写入 TCS 上的磁盘卷时的有效扩展构成了重大障碍。因此，在我们能够解决模拟引发的一些有趣问题之前，我们的 MRAC 分配就会耗尽。我们与 PSC 科学家 Troy Wymore 和 Shawn Brown 进行了深入讨论，他们强烈建议研究在 Cray XT3 上运行我们的系统模拟将提高扩展性和吞吐量的可能性。因此，我们希望请求在 XT3 上开发分配服务单元，以此来延长当前模拟的持续时间，并探索这一新 PSC 资源的功能，以更有效地利用未来超级计算机的时间。