Modeling Metal-Containing Biological Systems

含金属生物系统建模

• 批准号: 6583542
• 负责人: ROBERT B MURPHY
• 金额: $ 10万
• 依托单位: SCHRODINGER, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-01 至 2004-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6583542
• 关键词: DNA binding protein; bioengineering /biomedical engineering; biophysics; chemical models; computer program /software; computer simulation; computer system design /evaluation; ligands; metal complex; metal metabolism; metalloendopeptidases; molecular dynamics; quantum chemistry; receptor binding

DESCRIPTION (provided by applicant): Schrodinger's QSite is a mixed quantum mechanics/molecular mechanics (QM/MM) program specifically targeted to biological applications. QSite is based on a pairing of Jaguar [with its fast pseudospectral implementation of density functional theory (DFT) and other ab initio methods] and Impact (a protein modeling package which employs the OPLS-AA force field). As part of Schrodinger's First Discovery suite, which also includes Glide, a high-throughput docking program, and Liaison, a ligand-receptor binding energy program, QSite has already been demonstrated to be a powerful new tool for studying the reactive chemistry of metalloenzymes. Under this Phase I proposal, QSite's capabilities will be extended by adding a synchronous transit transition state search algorithm, completing the set of parameterized QM/MM interface cuts for amino acids, and parameterizing QM/MM cuts for nucleic acids. These developments will greatly enhance QSite's robustness in characterizing the reactive chemistry of bioinorganic systems, as well as extend the range of potential applications. A proof of concept study on ligand docking to a Zn matrix metalloproteinase will also be performed, demonstrating another potential role for the program in the lead optimization process.

描述（由申请人提供）：Schrodinger的Qsite是专门针对生物应用的混合量子力学/分子力学（QM/mm）程序。 Qsite基于Jaguar的配对[其快速的伪谱实现密度功能理论（DFT）和其他AB INTIB算法]和Impact（一种采用OPLS-AA力场的蛋白质建模软件包）。作为Schrodinger的第一个发现套件的一部分，该套件还包括Glide，一个高通量对接程序，以及配体受体结合能量程序联络程序，QSite已经被证明是研究Metalloenzymes反应性化学的有力新工具。在此I阶段提案下，Qsite的功能将通过添加同步过渡状态搜索算法来扩展，从而完成了用于氨基酸的参数化QM/mm界面切割的集合，并为核酸的参数化QM/mm切割。这些发展将大大增强Qsite在表征生物无机系统的反应性化学方面的鲁棒性，并扩展了潜在应用的范围。还将进行有关配体对接到Zn基质金属蛋白酶酶的概念验证研究，这证明了该程序在铅优化过程中的另一个潜在作用。