SOLVATION AND REACTION DYNAMICS OF BIOPOLYMERS

生物聚合物的溶解和反应动力学

• 批准号: 2186739
• 负责人: PETER Jacob ROSSKY
• 金额: $ 16.05万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-05-01 至 1998-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2186739
• 关键词: biophysics; chemical association; chemical bond; chemical hydration; chemical models; chemical stability; chymotrypsin; computer simulation; conformation; globular protein; hydrogen transport; hydropathy; insulin; intermolecular interaction; lysozyme; model design /development; molecular dynamics; molecular orbital; protein structure function; quantum chemistry; solubility; solvents; structural biology; thermodynamics; trypsin

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.

本文的研究主要集中在两个问题的理论研究上， 的基本意义，以阐明之间的关系， 生物聚合物的结构和功能。 这些是：1）发生 和生物化学衍生物的替代模式疏水 水化，和2）化学键重排相关的建模 具有酶活性，重点是质子转移。 疏水 互动被认为是一个主要的贡献者， 球状蛋白的构象稳定性和一个关键的驱动力， 涉及生物分子的关联现象，这一领域将是 最初的焦点。 具体来说，我们将探讨潜在的 通过水化的延伸或凹的疏水性发挥关键作用 结构设计背景下折叠多肽的表面区域 以及其在稳定性、溶解性和与其它物质的非键缔合中的作用 物种，包括酶底物。 数量意义 将通过自由能微扰计算进行检查。 研究 将通过计算机模拟一组选定的 多肽系统和特定的模型系统。 质子转移 是一种普遍存在的生化过程，存在于代谢催化和 跨细胞膜的主动运输。 在这第二个领域， 调查，我们将集中在我们最近的小说的发展， 半经验的，计划的共价相互作用的描述，在这个 生物物理背景。 模型的格式描述了相互作用 通过单独的局部键合和非键合相互作用， 以紧凑和计算快速的形式来表示每一个。 模型的成功开发将使媒体 动力学和核隧道效应纳入生物物理研究， 保持计算效率。初步申请将包括 对水和溶菌酶的反应。这些项目的实施将促进 我们对生物聚合物行为起源的理解， 通过计算定量评估这种行为的能力。