Structure Function Correlation of G-Proteins

G 蛋白的结构功能相关性

• 批准号: 9808638
• 负责人: Arieh Warshel
• 金额: $ 33万
• 依托单位: University of Southern California
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9808638&HistoricalAwards=false
• 关键词: Structure; Function; Correlation; Proteins

9808638 Warshel The combined Quantum Mechanical (ab initio)/ Langevin Dipoles (QM(ai)/LD) model developed in this laboratory will be used to obtain reliable free energy surfaces for phosphate hydrolysis in solution. This study will focus on validating the calculated surfaces by reproducing the main experimental results in the field. The validated and refined potential surfaces for the solution reaction will be used for calibrating Empirical Valence Bond (EVB) potential surfaces for studies of phosphate hydrolysis in proteins. The calibrated EVB surface will be used for interpolating the energetics of the solution reaction to protein environments and eventually for elucidating the actual mechanism of p21ras. Ab initio calculations and EVB modeling will be used in order to extract more unique mechanistic information from the emerging structure of G-proteins and their transition state analogs. GTP-binding proteins are involved in the regulation of cellular function in virtually all living organisms, and control signal transduction processes. Understanding the detailed actions of these proteins is one of the important current challenges of molecular biology. The studies of p21ras and other related G-proteins are undergoing a "structural revolution" from which new structures of G-proteins and their complexes with the corresponding accessory proteins are rapidly emerging. In addition, exciting information about the structure of G-proteins with their assumed transition state (TS) analogs is becoming available. This offers a unique opportunity for elucidating the detailed molecular mechanisms of the action of these proteins. The continuation of the structural revolution in the field of G-proteins provides an exciting opportunity for computer-aided structure-function analysis of these systems.

9808638 Warshel本实验室开发的组合量子力学（从头算）/朗之万偶极子（QM（ai）/LD）模型将用于获得溶液中磷酸盐水解的可靠自由能表面。 本研究将侧重于验证计算表面再现的主要实验结果在该领域。 经验证和细化的电位表面的溶液反应将用于校准经验价键（EVB）电位表面的磷酸盐水解蛋白质的研究。 校准的EVB表面将被用于内插的溶液反应的蛋白质环境的能量，并最终阐明p21 ras的实际机制。从头计算和EVB建模将被用于从G蛋白及其过渡态类似物的新兴结构中提取更多独特的机理信息。 GTP结合蛋白参与几乎所有生物体的细胞功能调节，并控制信号转导过程。 了解这些蛋白质的详细作用是分子生物学当前面临的重要挑战之一。 p21 ras和其他相关G蛋白的研究正在经历一场“结构革命”，新的G蛋白结构及其与相应辅助蛋白的复合物正在迅速出现。 此外，关于G蛋白及其假定的过渡态（TS）类似物的结构的令人兴奋的信息正在变得可用。 这为阐明这些蛋白质作用的详细分子机制提供了独特的机会。 G蛋白领域结构革命的继续为这些系统的计算机辅助结构-功能分析提供了令人兴奋的机会。