SOLVATION AND REACTION DYNAMICS OF BIOPOLYMERS

建议的研究集中在两个问题的理论研究上。 对阐明二者关系的根本意义 生物聚合物的结构和功能。这些是：1)发生 以及不同疏水模式的生化分支 水合作用，以及2)相关化学键重排的模拟 具有酶活性，重点是质子转移。疏水性 相互作用被认为是 球状蛋白质的构象稳定性和一个关键的驱动力 涉及生物分子的缔合现象，这一领域将是 主要的初始焦点。具体地说，我们将调查潜在的 延伸疏水或凹形疏水的水化作用 结构设计背景下折叠多肽的表面区 以及它在稳定性、溶解性和与其他化合物的非键结合中的作用 种类，包括酶底物。量的意义 将通过自由能微扰计算来检验。这些研究 将通过计算机模拟选定的一组 水中的多肽体系和特定的模型体系。质子转移 是代谢催化中普遍存在的一种生化过程 跨细胞膜的主动运输。在这第二个领域 调查，我们将重点关注我们最近小说的发展， 半经验的，用于描述本论文中共价相互作用的方案 生物物理背景。模型的格式描述了交互 通过单独的局部绑定和非绑定相互作用，能够 以紧凑和计算快速的形式表示每一个。 该模型的成功开发将使媒体能够被纳入 动力学和核隧道效应在生物物理研究中的应用 保持计算效率。初步申请将包括 对水和溶菌酶的影响。对这些项目的追求将增强 我们对生物聚合物行为起源的理解和我们的 通过计算对这种行为进行定量评估的能力。

The proposed research focuses on theoretical studies of two problems of fundamental significance to the elucidation of the relationship between the structure and function of biopolymers. These are : 1) the occurrence and biochemical ramifications of alternative modes of hydrophobic hydration, and 2) the modelling of chemical bond rearrangements associated with enzymatic activity, with emphasis on proton transfer. Hydrophobic interactions are recognized as a principal contributor to the conformational stability of globular proteins and a key driving force for association phenomena involving biomolecules, and this area will be the primary initial focus. Specifically, we will probe the potentially critical role played by hydration of extended or concave hydrophobic surface regions of folded polypeptides in the context of structural design and its role in stability, solubility and nonbonded association with other species, including enzymatic substrates. The quantitative significance will be examined via free energy perturbation calculations. The studies will be carried out by computer simulation of a selected set of polypeptide systems and specific model systems in water. Proton transfer is a ubiquitous biochemical process present in metabolic catalysis and in active transport across cell membranes. In this second area of investigation, we will focus on the development of our recent novel, semiempirical, scheme for the description of covalent interactions in this biophysical context. The format of the model describes interactions through separate local bonding and nonbonding interactions and is capable of representing each in compact and computationally rapid form. Successful development of the model will enable the inclusion of medium dynamics and nuclear tunnelling effects into biophysical studies with retention of computational efficiency. Initial applications will include those to water and to lysozyme. Pursuit of these projects will enhance both our understanding of the origins of biopolymer behavior and our ability to quantitatively evaluate this behavior computationally.