NEW METHODS FOR QUANTUM BIOCHEMISTRY IN SOLUTION

解决方案中的量子生物化学新方法

• 批准号: 2378284
• 负责人: Murco Ringnalda
• 金额: $ 37.5万
• 依托单位: SCHRODINGER, INC.
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-09-01 至 1998-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2378284
• 关键词: biochemistry; chemical kinetics; chemical models; chemical structure; computer simulation; computer system design /evaluation; drug receptors; hydrogen bond; intermolecular interaction; macromolecule; method development; molecular dynamics; molecular energy level; parallel processing; quantum chemistry; receptor binding; solutions

Ab initio quantum chemistry methods are now both accurate and practical when applied to gas phase calculations, but useful applications of these techniques to most biological and biomedical processes will not be feasible until they can be used for realistic and precise calculations of solvated systems. Schrodinger, Inc. proposes to use its PS-GVB code, a reliable and efficient general purpose ab initio electronic structure program, together with the self-consistent reaction field (SCRF) methodology developed in Phase I of this research, to treat complex biological systems in solution. The Phase II research described in this proposal will address the key barriers to routine use of computational methods for drug binding and other biomedical and biochemical applications. The accuracy of continuum models for solvated systems will be substantially improved with hydrogen bonding corrections. Schrodinger then plans to combine the SCRF code with the macromolecular simulation package MacroModel, simultaneously implementing recent advances in the use of multiple timescales in molecular dynamics. PROPOSED COMMERCIAL APPLICATION: The extensions of quantum mechanical computational methods described here will permit practical and inexpensive evaluations of the properties of candidate drug molecules. Consequently, we expect substantial commercial interest in this software, particularly from the pharmaceutical industry.

量子化学从头算方法现在既准确又实用 当应用于气相计算时，但是这些的有用应用 大多数生物和生物医学过程的技术将不会被 直到它们可以用于现实和精确的计算， 溶剂化系统 薛定谔公司建议使用其PS-GVB代码， 可靠和有效的通用从头算电子结构 自洽反应场（SCRF） 在本研究的第一阶段开发的方法，治疗复杂的 解决方案中的生物系统。 本提案中描述的第二阶段研究将解决关键问题， 常规使用药物结合计算方法的障碍， 其他生物医学和生物化学应用。 连续统的准确性 溶剂化系统的模型将大大改善与氢 键合校正。 薛定谔然后计划将SCRF代码与以下代码结合联合收割机 大分子模拟包MacroModel，同时 在使用多重时标方面取得的最新进展， 分子动力学 拟议的商业应用：量子力学的扩展 这里描述的计算方法将允许实用和廉价的 评价候选药物分子的性质。 因此，委员会认为， 我们预计这款软件会引起巨大的商业兴趣， 从制药行业。