SOFTWARE FOR DFT CALCULATIONS IN SOLUTION AND PROTEINS

描述：(改编自申请者的摘要)总体目标 这一建议的目的是提供一种卓越的计算工具 结构-功能关系的定量分析 蛋白质和水溶液中的化学反应和生化反应。 申请者计划通过将最先进的 计算量子力学方法(密度泛函理论， DFT)和最近开发的处理溶剂化效应的方法 基于经典静电学和连续介质理论。在第一阶段 将采取以下步骤来开发、验证和测试 软件：1)水化效果评价原型软件 关于溶液中的小量子力学系统将被开发和 用于水化能和溶液偶极矩的计算 可获得实验数据的小分子的；依赖性的 关于连续统理论的基组和参数的结果 将会被研究。(2)尽可能准确地陈述 电子密度是计算成功的关键， 将测试分布式多极分析(DMA)的高级方法 用离散傅里叶变换评估精确多极展开的效果 结果。(3)经典多极和原子极化率 类蛋白质介质将自我稳定地引入DFT 具有溶剂反应场以允许连续介质和原子 蛋白质活性部位环境的表示。(4)测试 将对丝氨酸的酶作用机理进行计算 将DFT结果与已发表的实验结果进行比较的蛋白酶 和理论研究。该系统将被简化，以使 在第一阶段的时间范围内可行的计算 求婚。(5)自主开发的原型软件 对其科学价值和商业价值的测试和评估 成立了研究小组和一家商业软件公司。这样的一个 Biosym公司对根据以下条款开发的软件的权利感兴趣 这个项目。

DESCRIPTION: (Adapted from the applicant's abstract) The general goal of this proposal is to provide a superior computational tool for quantitative analysis of the structure-function relationships in proteins and of chemical and biochemical reactions in aqueous solutions. The applicants plan to achieve this goal by combining the most advanced approach of computational quantum mechanics (Density Functional Theory, DFT) and recently developed methods of treatment of solvation effects based on classical electrostatics and continuum theory. In Phase I the following steps will be undertaken to develop, validate and test the software: 1) A prototype software for evaluation of hydration effects on small quantum mechanical systems in solution will be developed and applied to calculation of hydration energies and solution dipole moments of small molecules for which experimental data is available; dependence of the results on the basis sets and parameters of the continuum theory will be studied. (2) As accurate a representation as possible of the electron density is critical for the success of the computations, advanced methods of Distributed Multipole Analysis (DMA) will be tested with DFT to evaluate effects of accurate multipole expansion of the results.(3) Classical multipoles and atomic polarizabilities of a protein-like medium will be self consistently introduced into DFT along with the solvent reaction field to allow both continuum and atomic representations of the environments of protein active sites. (4) Test calculations will be performed for the enzymatic mechanism of serine proteases to compare DFT results with published results of experimental and theoretical studies. The system will be simplified to make computations feasible within the time frame of the Phase I of the proposal. (5) The prototype software will be given for independent testing and evaluation of its scientific and commercial merits to a few established research groups and a commercial software company. One such company, Biosym, is interested in rights for the software developed under this project.