COMPUTATIONAL ANALYSIS OF PEPTIDE/LIPID INTERACTIONS AND AT MEMBRANE SURFACES

肽/脂质相互作用和膜表面的计算分析

• 批准号: 7601291
• 负责人: DIANA MURRAY
• 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/7601291
• 关键词: Accounting; Award; Behavior; Binding; Biological; Biological Process; Cells; Cellular Membrane; Cellular biology; Characteristics; Collection; Computer Analysis; Computer Retrieval of Information on Scientific Projects Database; Disease; Dissection; Drug Design; Electrostatics; Event; Family; Funding; Grant; High Performance Computing; Hydrophobic Interactions; Institution; Lead; Length of Stay; Lipids; Macromolecular Complexes; Mediating; Membrane; Membrane Proteins; Methodology; Methods; Modeling; Molecular; Numbers; Operative Surgical Procedures; Peptides; Peripheral; Phospholipids; Productivity; Progress Reports; Property; Protein Family; Proteins; Protocols documentation; Range; Reporting; Research; Research Personnel; Resources; Site; Source; Students; Surface; System; United States National Institutes of Health; Viral; abstracting; base; computerized data processing; interest; physical property; programs; success

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. Keywords: Finite difference Poisson-Boltzmann, protein/lipid interactions, subcellular targeting, electrostatics, membranes Abstract: This is a request for an extension of the grant we were awarded beginning 10/01/04 by the NSF High-performance Computing and TeraGrid Sites Allocations Committee, number MCB030028 (also listed as PSC grant MCB020050P) for the period 10/01/04-09/30/05, with the possibility of the award continuing for three years. While this period has been an extremely productive one, we have significantly overdrafted this grant. As PI for this project, I take full responsibility for this and can only offer the explanations that 1) the resource was so well-suited to our computational needs that students and postdocs used it for additional projects not included in the original proposal, and 2) I was very ill this past year (including a major surgery and two hospital stays) and did not adequately impress upon the users in my lab the protocol for responsible usage. I deeply apologize for this situation, especially the latter, and it is my hope that this report, which briefly describes our increased usage and a new stringent usage protocol, will help convince the Allocations Committee to forgive the overdraft and grant us an extension of our current allocation for this period. Specifically, we are humbly asking for an additional 20,000 SU on the PSC HP Marvel above and beyond the ~ 100,000 SU already used to date and that we may still retain access to our TeraGrid Wide Roaming SUs. We would greatly appreciate a second chance and hope that we may be granted continued access to the HP Marvel through 09/30/04. I have simultaneously submitted a Progress Report which provides more detail on our current projects which are being supported by our NSF High-performance Computing award. This report also describes our productivity during this period. We have been using the TeraGrid PSC HP Marvel with great success in modeling multi-component macromolecular complexes of significant biological relevance. This resource is, thus, crucial to the success of our research program. As described in our original proposal, the long term objective of the proposed research is to characterize the structural and energetic basis for the binding of peripheral membrane proteins to phospholipid membranes and, in turn, to better understand the biophysical basis of membrane-mediated events in cells. The finite difference Poisson-Boltzmann (FDPB) method has proved extremely accurate in its ability to account for many of the experimentally determined electrostatic properties of protein/membrane systems, and we are applying this continuum method along with a semi-empirical approach to characterize the hydrophobic contribution to membrane association to the following problems. The specific aims of our original proposal seek to characterize the membrane binding behaviors of a collection of carefully selected families of peripheral membrane proteins. While each family has unique membrane binding behaviors, their membrane association can ultimately be described by the interplay of electrostatic and hydrophobic interactions. During the past year we have built on previous methodology to more accurately depict the physical properties of protein/membrane systems, and we have expanded our focus to include other protein families with their own interesting membrane binding characteristics. (Progress related to our original aims and proposed new projects are provided in our Progress Report.) A fundamental question in cell biology is how the recruitment of proteins to different cellular membranes is achieved and regulated. The major research objective in our lab is to use computational approaches to understand the physical, molecular and structural bases of membrane targeting in cellular signaling processes and in viral assembly. A detailed dissection of the molecular mechanisms underlying the membrane binding behaviors of a wide range of peripheral proteins would facilitate the understanding of subcellular targeting as well as the rational design of drugs that inhibit membrane binding in biological processes that lead to disease states.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 关键字： 有限的差异泊松 - 玻璃体，蛋白质/脂质相互作用，亚细胞靶向，静电，膜 抽象的： 这是向我们从04年10月10日开始授予我们授予赠款的请求，NSF高绩效计算和TERAGRID网站分配委员会，编号MCB030028（也被列为PSC Grant MCB020050P）在10/01/01/09/30/05期间授予奖励，并连续三年获得三年。尽管这一时期是一个极其富有成效的时期，但我们已经大大透支了这笔赠款。作为该项目的PI，我对此承担全部责任，只能提供以下解释：1）资源非常适合我们的计​​算需求，以至于学生和博士后将其用于原始建议中不包括的其他项目，而2）我今年我病得很厉害（包括一次重大手术和两次医院住院），并没有对我的一项责任的使用者给我的一份协议留下深刻的印象。我对这种情况深表歉意，尤其是后者，这是我希望这份报告简要描述了我们增加的用法和新的严格用法协议，这将有助于说服分配委员会原谅透支并授予我们当前分配此期间的分配。具体来说，我们谦虚地要求在PSC HP Marvel上额外增加20,000 SU，超出了约100,000 SU，但我们仍然可以保留对Teragrid宽漫游的SUS的访问权限。我们将非常感谢第二次机会，并希望我们能够在09/30/04之前继续访问HP Marvel。我同时提交了一份进度报告，该报告提供了我们当前项目的更多详细信息，而NSF高性能计算奖支持。该报告还描述了我们在此期间的生产力。我们一直在使用Teragrid PSC HP Marvel，在对具有重要生物学相关性的多组分大分子复合物进行建模方面取得了巨大成功。因此，该资源对于我们的研究计划的成功至关重要。如我们最初的建议中所述，所提出的研究的长期目标是表征周围膜蛋白与磷脂膜结合的结构和能量基础，进而更好地理解细胞中膜介导的事件的生物物理基础。事实证明，有限的差异泊松托泊尼（FDPB）方法非常准确地说明了蛋白质/膜系统的许多实验确定的静电性能，并且我们正在将这种连续方法以及一种半经验方法以及一种半经验方法来表征对以下问题对膜相关性的表征。我们原始建议的具体目的旨在表征一组精心选择的外围膜蛋白家族的膜结合行为。尽管每个家庭都有独特的膜结合行为，但最终可以通过静电和疏水相互作用的相互作用来描述它们的膜关联。在过去的一年中，我们建立了以前的方法，以更准确地描述蛋白质/膜系统的物理特性，并且我们将重点扩展到包括具有自己有趣的膜结合特性的其他蛋白质家族。 （在我们的进度报告中提供了与我们最初的目标和拟议的新项目相关的进展。）细胞生物学的一个基本问题是如何将蛋白质募集到不同的细胞膜中。我们实验室中的主要研究目标是使用计算方法来了解细胞信号传导过程中膜靶向的物理，分子和结构碱基和病毒组装中的靶标。多种外围蛋白质的膜结合行为的详细解剖学将促进对亚细胞靶向的理解，以及在导致疾病状态的生物学过程中抑制膜结合的药物的合理设计。