SOFTWARE FOR DFT CALCULATIONS IN SOLUTION AND PROTEINS

描述：（改编自申请人的摘要）总体目标 该建议的目的是提供一种上级计算工具， 结构-功能关系的定量分析 蛋白质以及水溶液中的化学和生物化学反应。 申请人计划通过结合最先进的 计算量子力学的方法（密度泛函理论， DFT）和最近发展的溶剂化效应的处理方法 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 将开发解决方案中的小型量子力学系统， 应用于水化能和溶液偶极矩的计算 有实验数据的小分子;依赖性 结果的基组和参数的连续统理论 将被研究。 (2)尽可能准确地表示 电子密度是计算成功的关键， 将测试分布式多极分析（DMA）的先进方法 用DFT来评估精确多极展开的影响， 结果(3)原子的经典多极子和原子极化率 蛋白质类介质将自洽地引入DFT沿着 与溶剂反应场，以允许连续和原子 蛋白质活性位点环境的表征。 (4)测试 计算将进行丝氨酸的酶机制 将DFT结果与已发表的实验结果进行比较 和理论研究。该系统将被简化， 在第一阶段的时间范围内可行的计算 提议 (5)原型软件将被独立地提供给 测试和评估其科学和商业价值，以少数 成立了研究小组和商业软件公司。 一个这样 公司，Biosym，是有兴趣的权利，为软件开发下 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.