BIOMOLECULAR INTERACTIONS AND ENZYMATIC PROCESSES

生物分子相互作用和酶促过程

• 批准号: 2684981
• 负责人: JIALI GAO
• 金额: $ 13.33万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-09-30 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2684981
• 关键词: abzyme; bacteriorhodopsins; computer program /software; computer simulation; dipole moment; enzyme mechanism; enzyme structure; intermolecular interaction; ionic bond; mathematical model; method development; model design /development; molecular dynamics; molecular polarity; molecular rearrangement; phosphomutase; photochemistry; physical model; protein structure function; quantum chemistry; structural biology; water solution

DESCRIPTION: A research project aimed at developing the capacity for theoretical characterization of biomolecular interactions and enzymatic processes in solution is proposed. The theoretical approach centers on computer simulations of proteins at the atomic level using molecular dynamics techniques. To provide an accurate description of intermolecular interactions for chemical and photochemical processes in biological systems, a combined quantum mechanical and molecular mechanical (QM/MM) approach is being developed. A key feature of the proposed method is the incorporation of a polarizable intermolecular potential function (PIPF) into the combined QM/MM method for both the ground and excited state calculations. Thus, condensed phase polarization effects on both the quantum-mechanically treated substrate molecule and the rest of the protein/solvent system will be consistently determined in the combined QM/PIPF approach. In addition, a localized bond orbital method will be used to improve and properly address the division of covalent bonds across the QM and MM regions for application in enzymatic processes. A major thrust will be investigations of the structure and dynamics of bacteriorhodopsin. A novel approach to the active site structural refinement of the membrane protein baceriorhodopsin is being developed. The procedure involves reproduction of the experimental absorption spectra and opsin shifts through molecular dynamics calculations using the combined Q< configuration interaction and PIPF method. The structural modeling will be followed by simulation of the primary photoisomerization reaction and proton translocation in bacteriorhodopsin through a series of excited-state trajectory and free- energy calculations. In addition, the Claisen rearrangement of chorismate to prephenate in chorismate mutase and in a catalytic antibody will be modeled to gain structural and electrostatic insight into enzyme catalysis. Initial studies will include determination of the potential of mean force for the reaction in aqueous solution and in the native protein. Subsequent work on the process in the catalytic antibody will lead to predictions of amino acid substitutions that may improve the catalytic efficiency of the catalytic antibody.

描述：旨在发展能力的研究项目 生物分子相互作用和酶促的理论表征 提出了解决方案中的过程。 理论方法以 使用分子在原子水平上对蛋白质进行计算机模拟 动力技术。 提供准确的描述 化学和光化学过程的分子间相互作用 生物系统，量子机械和分子的组合 正在开发机械（QM/mm）方法。 的关键特征 提出的方法是掺入可极化的分子 潜在函数（PIPF）到这两种合并的QM/mm方法中 地面和激发状态计算。 因此，凝结相 对两种量子力学处理的底物的极化影响 分子和其余的蛋白质/溶剂系统将始终如一 在组合的QM/PIPF方法中确定。 另外，本地化 债券轨道方法将用于改进并正确解决 跨QM和MM区域的共价债券划分用于应用 在酶促过程中。 主要的推力将是对结构和动力学的研究 细菌淡淡蛋白质。 一种新型的活性站点结构的方法 正在开发膜蛋白菌细菌淡淡蛋白质的细化。 该过程涉及实验吸收的繁殖 光谱和OPSIN使用分子动力学计算转移 组合的Q <配置交互和PIPF方法。 这 结构建模将随后模拟初级 光异构化反应和质子易位 通过一系列激发轨迹和自由 - 能量计算。 此外，乳腺酸盐的claisen重排在 为毒突变酶和催化抗体将被建模以获得 对酶催化的结构和静电洞察。 最初的 研究将包括确定平均力的潜力 水溶液和天然蛋白质中的反应。 随后的 在催化抗体中的过程中的工作将导致预测 可以提高催化效率的氨基酸取代 催化抗体。