THEORETICAL STUDIES ON THE DYNAMIC ASPECTS OF MACROMOLECULAR FUNCTION

一氧化氮在心肌缺血后的再结合动力学 光解离肌红蛋白是模拟使用的技术， 分子动力学 动力学进展曲线，通过平均 100轨迹，可以很好地再现了一个简单的模型， 朗之万粒子在平均力势中运动， 非反应性弹道 从能量阱中逃逸的速率 邻近血红素的值与从 实验数据表明，多孔模型提供了 非指数再结合动力学的合理解释。 一 布朗动力学算法，最初设计用于计算 扩散控制的反应速率，已被改编为计算 横向流体动力摩擦（即，的倒数 扩散系数）。 这项工作 效应利用了两个看似无关的物理之间的深刻类比， 量，并导致一种新颖的和高效的计算方法， 大分子的扩散系数。 有一种理论 为DNA分子电泳而开发， 微影构造的合成凝胶，其由 基本上是柱的二维规则阵列。 具体而言是 一个DNA分子被一个帖子钩住， 形成U形结构。 一致性良好 理论和实验之间的联系，表明 长度分级的机制可以在 微观水平。 本实验室开发的一种高效算法 计算大分子的静电性质， 应用于细胞色素c-细胞色素过氧化物酶系统，以阐明 静电相互作用对氧化还原电位的影响， 复合物形成的能量和电子转移的效率。 在 除了成功预测突变对那些 性质，这些计算揭示了结构的基础， 氧化还原电位和电子转移的速率是由 蛋白质环境

The kinetics of the geminate rebinding of nitric oxide following photodissociation to myoglobin was simulated using the technique of molecular dynamics. The kinetic progress curve, obtained by averaging 100 trajectories, could be well reproduced by a simple model of a Langevin particle moving in a potential of mean force calculated from nonreactive trajectories. The rate of escape from the energy well adjacent to the heme was in good agreement with the value calculated from experimental data, suggesting that a multiple-well model provides a plausible explanation for the nonexponential rebinding kinetics. A Brownian dynamics algorithm, originally devised for calculating diffusion-controlled reaction rates, has been adapted to calculate the transalational hydrodynamic friction (i.e., the reciprocal of the diffusion coefficient) of objects with complex shapes. This work in effect exploits a deep analogy between two seemingly unrelated physical quantities, and leads to a novel and highly efficient way of calculating the diffusion coefficients of macromolecules. A theory has been developed for the electrophoresis of DNA molecules in microlithographically constructed synthetic gels consisting of an essentially two dimensional regular array of posts. Specifically, the average "unhooking" time for a DNA molecule that got hooked on a post to form a U-shaped structure was calculated. Good agreement was found between theory and experiment, indicating that one fundamental aspect of the mechanism of length fractionation can be fully understood on a microscopic level. An efficient algorithm developed in this laboratory to calculate the electrostatic properties of macromolecules has been applied to the cytochrome c-cytochrome peroxidase system to elucidate the influence of electrostatic interactions on redox potentials, the free energy of complex formation and the efficiency of electron transfer. In addition to successfully predicting the effect of mutations on those properties, these calculations revealed the structural basis of how the redox potential and the rate of election transfer is controlled by the protein environment.