Distance Geometry Receptor Mapping

距离几何受体映射

• 批准号: 8705006
• 负责人: Gordon Crippen
• 金额: $ 24.5万
• 依托单位: Regents of the University of Michigan - Ann Arbor
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1991-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=8705006&HistoricalAwards=false
• 关键词: Distance; Geometry; Receptor; Mapping

Dr. Crippen is working on the problem of understanding the specific binding of small molecules to biological receptor macromolecules. It is preferable to determine directly the structure of such complexes but the required crystallographic and/or NMR studies are much more difficult to carry out than simply measuring the binding constant. What is needed is a method of objectively deducing receptor site geometry and energetics given only the binding constants for a series of compounds. The ideal method would be completely objective and independent of assumptions by the investigator. Dr. Crippen is continuing his development of mathematical models for receptor-ligand interactions. This involves the modelling of binding energies while allowing the ligands to assume their full range of energetically allowed conformations within the site. No one else is developing methods at this level of sophistication and it is clear that the models for proteins of known structure can be tested vis- a-vis experiment thus giving confidence in the model for unknown proteins.

克里彭博士正在研究如何理解小分子与生物受体大分子的具体结合。直接确定这种配合物的结构是可取的，但所需的晶体学和/或核磁共振研究比简单地测量结合常数要困难得多。所需要的是一种客观地推导受体位置几何和能量学的方法，只给出一系列化合物的结合常数。理想的方法应该是完全客观的，独立于研究者的假设。克里彭博士正在继续发展受体-配体相互作用的数学模型。这涉及到结合能的建模，同时允许配体在位点内承担其能量允许的全部构象。没有人在开发这种复杂程度的方法，很明显，已知结构的蛋白质模型可以通过面对面的实验进行测试，因此对未知蛋白质的模型有信心。