SIMULATION OF HEAT CAPACITIES OF PROTEINS

热容量（Cp）效应已在 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 对蛋白质折叠和蛋白质-DNA结合的能量学的剖析。最 热容效应来自大分子-溶剂相互作用。溶剂 对于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，例如极性和非极性的相反符号 水化Cp在基本水平上仍然无法解释。经验领域和 组相关分析被广泛用于分离出Cp贡献， 蛋白质，但没有更好的理论理解，不知道什么时候 这种方法在蛋白质和DNA的复杂环境中可能失败。 该项目旨在解决方法上的一些差距， 理解，特别是使用基于组合的方法， 随机网络（RN）和显式水模型，以了解水化Cp 在数量和分子水平上发生变化。先前使用RN的研究 极性和非极性溶质的模型已经表明i）为什么，在变化方面， 在溶质周围的水结构中， 极性溶剂化具有相反的符号ii）该方法可用于 溶质-溶剂热容量效应的定量研究。继续进行 夏普博士的目标是研究含有极性和非极性基团的化合物 Cp的可加性，不同水化壳层的竞争 群体之间的相互作用，以及加和性假设是否以及何时可能崩溃。在 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比简单的面积或组方法更准确， 但不涉及每个系统的显式水模拟。的方法 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熵的平衡， 相互作用，以及溶剂化和分子间能量的平衡。（三） 抗冻蛋白（AEP）周围的水的分析。这将用于 解决什么是AFP的独特属性及其 与水的相互作用使其具有防冻剂的功能。（四） 该方法也将扩展到水化G、S和H的计算。一个 这种类型隐式溶剂化模型在大分子中有许多用途 仿真。蛋白质-DNA相互作用的研究可直接应用于 更好地理解基因调控，这反过来又有许多应用， 了解正常和疾病状态下的细胞功能。

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.