BIOMOLECULAR INTERACTIONS AND ENZYMATIC PROCESSES

说明：一个研究项目，旨在发展能力， 生物分子相互作用和酶的理论表征 解决方案中的过程。 理论方法的核心是 使用分子计算机模拟蛋白质在原子水平上 动力学技术 提供对…的准确描述 化学和光化学过程的分子间相互作用 生物系统，结合了量子力学和分子 机械（QM/MM）方法正在开发中。 的关键特征 所提出的方法是将可极化的分子间 潜在的功能（PIPF）到组合的QM/MM方法， 基态和激发态计算。 因此，凝聚相 极化效应的量子力学处理的基板 分子和蛋白质/溶剂系统的其余部分将一致地 在结合QM/PIPF方法中确定。 此外，本地化的 键轨道方法将被用来改善和妥善处理 跨QM和MM区域的共价键的划分以用于应用 在酶促过程中。 一个主要的推动力将是调查的结构和动力学， 细菌视紫红质 活性中心结构的新方法 正在开发膜蛋白细菌视紫红质的精制。 该过程涉及实验吸收的再现 光谱和视蛋白位移通过分子动力学计算， Q<组态相互作用与PIPF方法的结合。 的 结构建模之后将进行主要的模拟 光异构化反应和质子迁移 细菌视紫红质通过一系列的激发态轨迹和自由- 能源计算。 此外，还研究了分支酸盐到预苯酸盐的Claisen重排反应。 分支酸盐和催化抗体将被建模，以获得 结构和静电洞察酶催化。 初始 研究将包括确定平均力的潜力， 在水溶液和天然蛋白质中的反应。 后续 在催化抗体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 催化性抗体

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.