MOLECULAR MODELLING AND DRUG DESIGN BY COMPUTER

计算机分子建模和药物设计

• 批准号: 3838043
• 负责人: G W MILNE
• 金额: --
• 依托单位: DIVISION OF CANCER TREATMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3838043
• 关键词: DNA binding protein; RNA directed DNA polymerase; X ray crystallography; chemical models; chemical registry /resource; chemical structure function; computer simulation; drug design /synthesis /production; drug receptors; enzyme inhibitors; model design /development; phorbols; protein kinase C; protein tyrosine kinase; reverse transcriptase inhibitors

The techniques of computer-assisted molecular modeling have been applied to a variety of problems in the Laboratory of Medicinal Chemistry. Pharmacophore detection and analysis is a standard task, as is analysis of receptor sites and discovery of new lead compounds having known pharmacophores. Modeling Studies: Molecular models of a large number of compounds from the NCI database have been compared to the x-ray structures and the differences identified and rationalized. Protein Kinase C: Compounds that possess the correct pharmacophore and which can activate protein kinase C continue to be discovered. Some particularly potent phorbol competitors have been identified. Modeling of the structure of the zinc finger regions of protein kinase C has begun. Tyrosine Protein Kinase: A set of structural requirements for the inhibition of tyrosine protein kinase has been delineated and used in searches of the 3D database to identify several new lead compounds. Reverse Transcriptase Inhibitors: A large series of fluorine-containing dideoxynucleosides has been modeled and some of the structural requirements for RT inhibition have been identified. Three-Dimensional Database: Conversion of the NCI database from 2-D to 3-D coordinates is now well advanced. A new structure building program, CHEM-X, has been acquired and installed and has been found to give superior results to those obtained using CONCORD.

计算机辅助分子模拟技术已被应用 药物化学实验室的各种问题。 药效团检测和分析是一项标准任务， 受体位点和发现新的先导化合物， 药效团 建模研究：大量化合物的分子模型， NCI数据库已经与X射线结构进行了比较， 找出差异并加以合理化。 蛋白激酶C：具有正确药效团且 能够激活蛋白激酶C的物质不断被发现。 一些 已经鉴定了特别有效的佛波醇竞争者。 建模 蛋白激酶C的锌指区的结构 开始. 酪氨酸蛋白激酶：一组结构要求， 酪氨酸蛋白激酶的抑制已经被描述并用于 搜索3D数据库以识别几种新的先导化合物。 逆转录酶抑制剂：一大系列含氟 双脱氧核苷已被建模和一些结构 已经确定了RT抑制的要求。 三维数据库：NCI数据库从二维到三维的转换 3D坐标现在已经很先进了。 一个新的结构建设计划， CHEM-X，已获得和安装，并已发现， 上级结果优于使用CONCORD获得的结果。