COMPUTATIONAL STUDIES OF BIOMOLECULAR SYSTEMS

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。 我们实验室研究的总体目标是了解生物功能的结构、动力学和能量基础。我们实验室的工作包括几个生物系统的分子模拟和计算研究。1.研究了中性脂类和负电荷脂类组成的混合膜的聚集体性质。分子模拟和FEP模拟被用来评估脂质聚集的基本能量学基础和蛋白质与脂质结合的能量学。2.研究了PIP2调节内向整流钾通道的分子基础。布朗动力学模拟确定了PIP2结合在通道上的位置，而四聚体在磷脂膜上的MD模拟被用来定义PIP2诱导的通道开放的动力学和能量学。3.用模拟和自由能方法研究了自身免疫原肽与主要组织相容性复合体(MHC)蛋白的选择性。水在多肽MHC复合体与T细胞受体结合中的作用通过大规范蒙特卡罗模拟进行了研究。4.分子动力学模拟用于确定VIIa因子变构调节的基础，VIIa因子是一种在凝血途径中起重要作用的丝氨酸蛋白酶。组合基本动力学被用来确定变构激活和抑制的结构和能量基础。5.甜味感受器的同源建模产生了用于对接和模拟的模型。这些研究预测了通过实验技术测试的细胞外域和跨膜域中的结合口袋。

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.