PREDICTION OF WATER BINDING SITES IN ENZYME & INHIBITOR COMPLEXES

酶中水结合位点的预测

• 批准号: 6280165
• 负责人: STEPHEN DEBOLT
• 金额: $ 0.01万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6280165
• 关键词: biological products; biomedical resource; enzymes; lipids; proteins; technology /technique

My most recent studies involve the development, parameterization, and testing of atom level molecular mechanical interaction potentials. The interaction potential is being designed specifically for use in de novo predictions of the location of explicit water molecules in enzyme/inhibitor complexes. It is being tested on a database of "knowns", complexes compiled from the Brookhaven Protein Data Base. A search of the UCSF Computer Graphics Lab's well organized and indexed version of the PDB (o find high resolution enzyme/inhibitor complexes) was extremely helpful in getting this research off to a strong start. Now that the project is well towards completion, I have just recently used the CGL database to help me determine which enzyme/ligand complex structures will serve as "unknowns" for testing the water placement algorithm. Our recent work demonstrates the influence of bound water molecules at the active site complex of protein FKBP and the competitively bound solvent DMSO. Other recent studies include the development and testing of a water molecule placement algorithm. The UCSF Computer Graphics Laboratory provides an essential graphic and communications network link between the UCSF Pharmaceutical Chemistry Department and offsite investigators like myself. The CGL facilitates ongoing collaborations between researchers physically located at UCSF with those like myself at corporate research institutions by permitting visual assessment of shared online structural data, such as the orientations of computer simulated molecules, prediction of protein secondary structure, for monitoring solute/solvent and protein structures time-trajectories, and for appraisal of the accuracy of the configurations generated. The CGL technology also serves an essential role in helping collaborating me prepare graphics for scientific presentations and publications.

我最近的研究包括发展，参数化， 以及原子级分子力学相互作用势的测试。 相互作用势是专门设计用于 novo预测的位置明确的水分子在 酶/抑制剂复合物。 它正在一个数据库上进行测试， “knowns”，从Brookhaven蛋白质数据库编译的复合物。 一 搜索UCSF计算机图形实验室的良好组织和索引 PDB的版本（以找到高分辨率的酶/抑制剂复合物） 对这项研究有很大的帮助 现在，该项目已接近完成，我最近刚刚 我使用CGL数据库来帮助我确定哪种酶/配体复合物 结构将作为“未知数”测试水的位置， 算法 我们最近的工作证明了束缚水的影响 分子在蛋白质FKBP的活性位点复合物和 竞争性结合溶剂DMSO。 最近的其他研究包括 水分子放置算法的开发和测试。 的 UCSF计算机图形实验室提供了一个基本的图形和 UCSF药物化学之间的通信网络链接 部门和像我这样的非现场调查员。 CGL促进 加州大学旧金山分校的研究人员之间正在进行的合作 与企业研究机构中像我这样的人一起， 允许对共享的在线结构数据进行可视化评估，例如 计算机模拟分子的取向， 蛋白质二级结构，用于监测溶质/溶剂和蛋白质 结构的时间轨迹，并评估的准确性， 生成的配置。 CGL技术还提供了一个重要的 帮助我为科学研究准备图形 演讲和出版物。