SIMULATION OF HEAT CAPACITIES OF PROTEINS

热容(Cp)效应在 对蛋白质测定中疏水效应的认识 稳定性作为温度和氨基酸组成的函数，并且在 蛋白质折叠和蛋白质-DNA结合的能量学剖析。多数 热容效应来自于大分子与溶剂的相互作用。溶剂剂 对蛋白质的贡献在实验上得到了很好的表征，但即使是 最简单的特征，例如极点和非极点的相反符号 水合作用Cp，在基本水平上仍未得到解释。经验区和 组相关性分析被广泛用于区分CP在 蛋白质，但如果没有更好的理论理解，就不知道什么时候 这种方法在蛋白质和DNA的复杂环境中可能会失败。 该项目旨在解决方法和方法方面的一些差距 理解，具体地说是使用一种基于 用随机网络(RN)和显式水模型了解吸水作用CP 在数量和分子水平上的变化。以前使用RN的研究 关于极性和非极性溶质的模型已经说明了i)为什么，在变化方面 在水结构周围的溶质，其水化热容为非极 而极性溶剂化具有相反的符号II)，表明该方法可用于 溶质-溶剂热容效应的定量研究。继续进行 夏普博士的目标是研究同时含有极性和非极性基团的化合物 CP的可加性，如何竞争水化壳的不同 群体相互作用，如果以及何时加性假设可能会崩溃。在……里面 在这些研究的过程中，夏普博士的目标是i)开发一种快速的方法 计算水化Cp比简单的面积或分组方法更准确， 但不涉及每个系统的显式水模拟。本发明公开了一种用于 计算水合CP将应用于II)核酸-蛋白质结合， 为了更好地理解熵和热焓的平衡 相互作用，以及溶剂化和分子间能量的平衡。Iii) 抗冻蛋白(AEP)周围水的分析。这将被用来 回答以下问题：AFP的独特特性是什么？ 与水的相互作用使其起到防冻剂的作用。四) 这种方法也将推广到G，S和H。 这种隐式溶剂化模型在大分子研究中有着广泛的应用 模拟。蛋白质-DNA相互作用的研究直接应用于 更好地理解基因调控，这反过来又有许多应用 了解细胞在正常和疾病状态下的功能。

Heat capacity (Cp) effects have assumed a central importance in the understanding of the hydrophobic effect, in the determination of protein stability as a function of temperature and amino acid composition, and in the dissection of the energetics of protein folding and protein-DNA binding. Most heat capacity effects come from macromolecule-solvent interactions. The solvent contribution is well characterized experimentally for proteins, but even the simplest features, such as the opposite sign of the polar and nonpolar hydration Cp, remain unexplained at a fundamental level. Empirical area and group dependence analyses are widely used to separate out Cp contributions in proteins, but without a better theoretical understanding, it is not known when such approaches may fail in the complex environment of proteins and DNA. This project is designed to address some of these gaps in methodology and understanding, specifically to use a method based on a combination of the random network (RN) and explicit water models to understand hydraption Cp changes at a quantitative and molecular level. Previous studies using the RN model on a polar and a nonpolar solute have shown i) why, in terms of changes in water structure around the solute, the hydration heat capacity for apolar and polar solvation is of opposite signs ii) that the method can be used for quantitative study of solute-solvent heat capacity effects. Proceeding with compounds that contain both polar and non-polar groups Dr. Sharp aims to study the additivity of Cp, how the competing hydration shells of the different groups interact, and if and when the additivity assumptions might breakdown. In the course of these studies, Dr. Sharp aims to i) develop a rapid way to calculate hydration Cp that is more accurate than simple area or group methods, but does not involve explicit water simulations for each system. The method for calculating hydration cp will be applied to ii) nucleic acid-protein binding, in order to better understand the balance of entropic and enthalpic interactions, and the balance of solvation and intermolecular energies. iii) analysis of the water around antifreeze proteins (AEP). This will be used to address the question of what are the unique properties of AFP and its interaction with water that allow it to function as an antifreeze. iv) The approach will also be extended to calculation of hydration G, S & H. An implicit solvation model of this type has many uses in macromolecular simulations. The study of protein-DNA interactions has direct applications to a better understanding of gene regulation, which in turn has many applications to understanding cellular function in normal and diseased states.