Ensemble Docking Interrogates Structural Determinants of Ligand-Protein Interactions

整体对接探讨配体-蛋白质相互作用的结构决定因素

• 批准号: 1305874
• 负责人: Jens Meiler
• 金额: $ 40万
• 依托单位: Vanderbilt University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1305874&HistoricalAwards=false
• 关键词: Ensemble; Docking; Interrogates; Structural; Determinants

With this award, the Chemistry of Life Processes Program in the Chemistry Division at NSF is supporting the work of Dr. Jens Meiler of Vanderbilt university on an international collaborative effort to develop a new and potentially generally useful ensemble docking method for the RosettaLigand molecular modeling program. The German team inthis collaboration will be led by Drs. Annette Beck-Sickinger and Torsten Schoenefeld at U. Leipzig and will be supported by the DFG (Deutsche Forschungsgemeinschaft), and represents the experimental side of the collaboration. The ensemble docking approach to be taken involves simultaneous docking of multiple ligands while considering experimental SAR (Structure-Activity Relationships) as part of the scoring function. The collaborative team has selected the family of G-protein-coupled 7-(helix) transmembrane receptors (GPCRs) and ligand candidates as a platform upon which to develop this methodology. The German partnering team will take a natural product-inspired approach to ligand development/binding assessment for these receptors. Given the importance of protein-membrane receptor interactions across chemical biology, the proposed research aims at developing in silico methodology with potentially broad applicability to the community. Indeed success here and the possibility for disseminating the envisioned RosettaEnsembleDock module to the community would constitute arguably the most important scientific broader impact of this collaborative effort. The importance of GPCRs in signal transduction in biology cannot be overstated and therefore the model system upon which this computational algorithm is being built is also of considerable significance. The project will provide for interdisciplinary and international student training and exchange, and for the synergistic interaction of experimental protein-ligand binding team in Germany with a computational modeling/algorithm development team in the United States.

有了这个奖项，NSF化学部的生命过程化学计划正在支持范德比尔特大学的Jens Meiler博士的工作，该工作是一项国际合作努力，为RosettaLigand分子建模计划开发一种新的和潜在的普遍有用的系综对接方法。 这项合作中的德国团队将由美国大学的安妮特·贝克-西金格博士和托尔斯滕·舍内费尔德博士领导。莱比锡，将得到DFG（德国研究共同体）的支持，并代表合作的实验方面。 要采取的系综对接方法涉及多个配体的同时对接，同时考虑实验SAR（结构-活性关系）作为评分函数的一部分。合作团队选择了G蛋白偶联7-（螺旋）跨膜受体（GPCR）和配体候选物家族作为开发这种方法的平台。 德国合作团队将采用天然产物启发的方法来开发这些受体的配体/结合评估。 鉴于蛋白质-膜受体相互作用在化学生物学中的重要性，拟议的研究旨在开发具有潜在广泛适用性的计算机方法。 事实上，这里的成功和向社区传播设想的RosettaEnsembleDock模块的可能性将构成这种合作努力最重要的科学影响。 GPCR在生物学信号转导中的重要性怎么强调都不过分，因此建立这种计算算法的模型系统也具有相当大的意义。 该项目将提供跨学科和国际学生的培训和交流，并为协同作用的实验蛋白质-配体结合团队在德国与计算建模/算法开发团队在美国。