BIOMOLECULAR INTERACTIONS AND ENZYMATIC PROCESSES

描述：一个研究项目，旨在发展 生物分子相互作用和酶的理论表征 提出了解决方案中的过程。理论方法主要集中在 利用分子在原子水平上对蛋白质进行计算机模拟 动力学技术。提供准确的描述 化学和光化学过程中的分子间相互作用 生物系统，一个量子力学和分子相结合的系统 正在开发机械(QM/MM)方法。的一项关键功能 提出的方法是结合一种可极化的分子间 势函数(PIPF)引入QM/MM组合方法 基态和激发态计算。因此，凝聚相 量子力学处理的衬底上的极化效应 分子和蛋白质/溶剂系统的其余部分将一致地 在QM/PIPF组合方法中确定。此外，本地化的 将使用键轨道方法来改进和妥善解决 用于应用的QM和MM区域的共价键的划分 在酶过程中。 一个主要的推动力将是对宇宙的结构和动力学的研究 细菌视紫红质。一种新的活性部位结构分析方法 膜蛋白杆状视紫红质的精制正在开发中。 该过程涉及实验吸收的复制。 通过分子动力学计算的光谱和视蛋白位移 Q&lt；组态相互作用和PIPF方法相结合。这个 在结构建模之后，将对主要的 光致异构化反应和质子转移 细菌视紫红质通过一系列激发态轨迹和游离态. 能量计算。 此外，分支酸的Claisen重排在 分支酸变位酶和在一种催化抗体将模型化获得 对酶催化的结构和静电洞察。首字母 研究将包括确定平均作用力的潜力 在水溶液和天然蛋白质中的反应。后续 对催化抗体中这一过程的研究将导致预测 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.