COMPUTATIONAL STUDIES OF BIOMOLECULAR SYSTEMS

生物分子系统的计算研究

• 批准号: 7601431
• 负责人: ROMAN OSMAN
• 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/7601431
• 关键词: Allosteric Regulation; Binding; Biological; Biological Process; Blood coagulation; Charge; Complex; Computer Retrieval of Information on Scientific Projects Database; Docking; Factor VIIa; Free Energy; Funding; Goals; Grant; Homology Modeling; Institution; Laboratories; Lipids; Major Histocompatibility Complex; Membrane; Methods; Modeling; Molecular; Pathway interactions; Peptides; Phosphatidylinositol 4,5-Diphosphate; Phospholipids; Potassium Channel; Property; Proteins; Regulation; Research; Research Personnel; Resources; Role; Serine Protease; Site; Source; System; T-Cell Receptor; Testing; Transmembrane Domain; United States National Institutes of Health; Water; Work; base; computer studies; extracellular; receptor; simulation; sweet taste perception

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. The overall goal of the research in our lab is directed towards the understanding of the structural, dynamic and energetic basis for biological function. The work in our laboratory encompasses molecular simulations and computational studies of several biological systems. 1. We investigate the aggregations properties of mixed membranes composed of neutral and negatively charged lipids. Molecular and FEP simulations are used to assess the fundamental energetic basis for lipid aggregation and the energetics of protein association with lipids. 2. We study the molecular basis of PIP2 regulation of inward rectifying K-channels. Brownian dynamics simulations identified the sites of PIP2 binding on the channel and MD simulations of the tetramer in phospholipid membrane are used to define the dynamics and energetics of PIP2-induced channel opening. 3. The selectivity of autoimmunogenic peptides with Major Histocompatibility Complex (MHC) proteins is studied by simulations and free energy methods. The role of water in the association of the peptideMHC complex with the T-cell receptor is investigated by Grand Canonical Monte Carlo simulations. 4. MD simulations are used to define the basis for allosteric regulation of factor VIIa - a serine protease important in the blood coagulation pathway. Combined essential dynamics is used to identify the structural and energetic basis for allosteric activation and inhibition. 5. Homology modeling of sweet taste receptors produced models that are used in docking and simulations. These studies predicted the binding pockets in the extracellular and transmembrane domains that were tested by experimental techiniques.

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。子项目和 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。 我们实验室研究的总体目标是了解生物功能的结构、动态和能量基础。我们实验室的工作包括多个生物系统的分子模拟和计算研究。 1. 我们研究了由中性和带负电脂质组成的混合膜的聚集特性。分子和 FEP 模拟用于评估脂质聚集的基本能量基础以及蛋白质与脂质关联的能量学。 2. 我们研究了PIP2调节内向整流K通道的分子基础。布朗动力学模拟确定了 PIP2 在通道上结合的位点，并且磷脂膜中四聚体的 MD 模拟用于定义 PIP2 诱导的通道开放的动力学和能量学。 3.通过模拟和自由能方法研究了自身免疫原性肽与主要组织相容性复合体(MHC)蛋白的选择性。通过大正则蒙特卡罗模拟研究了水在肽 MHC 复合物与 T 细胞受体结合中的作用。 4. MD 模拟用于定义因子 VIIa（一种在凝血途径中重要的丝氨酸蛋白酶）变构调节的基础。组合的基本动力学用于确定变构激活和抑制的结构和能量基础。 5. 甜味受体同源建模产生用于对接和模拟的模型。这些研究预测了细胞外和跨膜结构域中的结合袋，并通过实验技术进行了测试。