FLEXIBLE DOCKING USING MODAL METHODS

使用模态方法进行灵活对接

• 批准号: 2718041
• 负责人: HON M CHUN
• 金额: $ 38.56万
• 依托单位: MOLDYN, INC.
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-03-15 至 2000-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2718041
• 关键词: bioengineering /biomedical engineering; chemical information system; computer program /software; computer simulation; computer system design /evaluation; drug design /synthesis /production; intermolecular interaction; ligands; molecular dynamics; physical model; receptor binding

The long term objective of this project is to develop a new ligand-receptor docking simulation software code, known as FLEX-DOCK, that features significant improvements in physical realism over current rigid-body docking codes (e.g., DOCK). It is intended to be used as a higher level filter to fill the gap between high speed low fidelity massive data base screening tools and much higher fidelity molecular dynamics modeling or direct laboratory screening via combinatorial chemistry techniques. FLEX-DOCK models the ligand and receptor active site as bodies (groups of atoms) with structural flexibility (degrees-of-freedom) described by component modes. The component mode framework facilitates structural flexibility for both ligand and receptor during the docking simulation. When completed, FLEX-DOCK will enable physically realistic and efficient screening in drug discovery that will result in much higher probability-for-success lead compounds entering the wet chemistry phase than possible from current docking simulation methods. The objectives for Phase II include: (1) completing the development of FLEX-DOCK's modal flexibility for ligand and receptor; and (2) developing a method for generating and storing FLEX-DOCK fbody prescriptions and component modes in the small molecule/ligand data bases that are used for screening in the pharmaceutical industry. PROPOSED COMMERCIAL APPLICATIONS: The improved realism of FLEX-DOCK over current rigid-body docking codes offers to significantly improve the efficiency of lead compound searches for drug design in the pharmaceutical industry. Two commercial applications are planned to take advantage of this opportunity: (1) commercial FLEX-DOCK software, which will be licensed and sold through a computational chemistry software firm; and (2) research services using FLEX-DOCK in support of drug design research for pharmaceutical firm customers.

该项目的长期目标是开发一种新的 配体-受体对接模拟软件代码，称为FLEX-DOCK， 在物理真实性方面比目前的 刚体对接代码（例如，DOCK）。 它旨在用作 更高级别的过滤器，以填补高速低保真度之间的差距 大量数据库筛选工具和更高保真度的分子 动力学建模或直接实验室筛选通过组合 化学技术 FLEX-DOCK模拟配体和受体活性 作为具有结构灵活性的体（原子团）的位点 （自由度）由组件模式描述。 组件模式 框架有利于配体和受体的结构灵活性 在对接模拟中。 完成后，FLEX-DOCK将启用 在药物发现中进行物理上现实和有效的筛选， 导致更高的成功概率铅化合物进入 湿化学阶段比可能从目前的对接模拟方法。 第二阶段的目标包括：（1）完成 FLEX-DOCK对配体和受体的模态灵活性;以及（2）开发 一种用于生成和存储FLEX-DOCK车身处方的方法， 小分子/配体数据库中的组件模式，用于 筛选在制药行业。 建议的商业应用：改进的FLEX-DOCK的真实感， 目前的刚体对接代码提供了显着改善 先导化合物在药物设计中的有效性 行业 两个商业应用程序计划利用 这个机会：（1）商业FLEX-DOCK软件，将是 通过计算化学软件公司许可和销售;以及（2） 使用FLEX-DOCK支持药物设计研究的研究服务， 制药公司的客户。