Theoretical Studies of Metalloprotein Chromophores

金属蛋白发色团的理论研究

基本信息

批准号：
7494180
负责人：
RICHARD A FRIESNER
金额：
$ 8.15万
依托单位：
COLUMBIA UNIV NEW YORK MORNINGSIDE
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-07-01 至 2008-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7494180
关键词：
Active Sites Algorithms Antineoplastic Agents Area Binding Biochemical Biological Biological Process Chemicals Chemistry Cisplatin Communities Complex Computer Simulation Computer software Cytochrome P450 DNA Development Drug Interactions Environment Evaluation Free Energy Goals Grant Hemerythrin Hemoglobin Investigation Ionic Strengths Iron Iron-Sulfur Proteins Ligand Binding Mechanics Metalloproteins Metals Methane hydroxylase Methodology Methods Modeling Myoglobin Nucleic Acids Numbers Oxidation-Reduction Oxidoreductase Progress Reports Protein Region Proteins Quantum Mechanics Reaction Research Ribonucleotide Reductase Sampling Solvents Structure Sulfur System Techniques Technology Testing Theoretical Studies Work chromophore conformational conversion density enthalpy improved interest method development molecular mechanics new technology novel strategies programs quantum quantum chemistry simulation user-friendly validation studies

项目摘要

This project has two major objectives (1) development of new technology for computational modeling of metalloprotein active sites; (2) application of the methods to biologically important problems. Methodology development is focused ab initio quantum chemistry, mixed quantum mechanical/classical mechanical simulation techniques, continuum solvation models, evaluation of free energy differences, and new algorithms for sampling large scale conformational changes. Metalloproteins to be studied in this granting period include methane monooxygenase, hemerythrin, cytochrome P450, myoglobin, hemoglobin, ribonucelotide reductase, and various iron-sulfur I Proteins. We also propose to initiate an effort to apply our method to the study of small metal Icontaining molecules, such as cisplatin (a major anticancer drug), binding to DNA. Results to be Iobtained from the calculations include characterization of reactant and product structures, reactive lintermediates, and transition states at an atomic level of detail, as well as computation of enthalpies land free energies for these various species.

该项目有两个主要目标（1）开发用于计算的新技术金属蛋白活性位点的建模；（2）将方法应用于生物学重要的问题。方法开发集中于量子化学，混合量子机械/经典的机械仿真技术，连续溶剂化模型，评估自由能差和用于对大规模构象变化进行采样的新算法。在此授予期间要研究的金属蛋白包括甲烷单加氧酶，HemeryThrin，细胞色素P450，肌红蛋白，血红蛋白，核糖核苷酸还原酶和各种铁硫我蛋白质。我们还建议努力将我们的方法应用于小金属的研究与DNA结合的偶像分子，例如顺铂（一种主要的抗癌药物）。结果从计算中进行的iObting包括反应物和产品结构的表征，反应性 lintermediates和过渡状态在原子能层面上，以及焓的计算这些各种物种的自由能量。