MOLECULAR MODELLING AND DRUG DESIGN BY COMPUTER

计算机分子建模和药物设计

• 批准号: 3853166
• 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/3853166
• 关键词: RNA directed DNA polymerase; chemical information system; chemical models; chemical structure function; computer assisted sequence analysis; computer simulation; drug design /synthesis /production; enzyme inhibitors; model design /development; protein kinase C; protein tyrosine kinase; reverse transcriptase inhibitors; solutions

The capabilities of computer-assisted molecular modeling have been expanded in a variety of directions and the techniques have been applied to a number of problems in the LMC concerning drug design, receptor sites, binding to-and inhibition of enzymes. Modeling Studies: The effect of solvent on the stable conformations of various medicinally important molecules has been studied and some understanding of the conformation in solution has been secured. Protein Kinase C: Inhibition of the binding of phorbol to protein kinase C was observed with several ribose-derived gamma-lactones as indicated by models of the compounds. Tyrosine Kinase: The structural requirements in the styrene series for successful inhibition of tyrosine kinase have been established and tested. Reverse Transcriptase Inhibitors: A study of the ring-expanded oxetanocins was completed. One of the synthesized isomers showed anti-HIV activity and the other did not. This result was compatible with the modeling data. Three-Dimensional Database: Approximately half the compounds in the DTP Database have been converted to three-dimensional structures and a distance-based search system has been developed.

计算机辅助分子建模的能力已经被 在不同的方向扩展，这些技术已经被应用 LMC中有关药物设计、受体的若干问题 酶的结合和抑制。 模拟研究：溶剂对化合物稳定构象的影响 已经研究了各种医学上重要的分子，其中一些 对溶液中的构象的了解已经得到保证。 蛋白激酶C：佛波醇与蛋白激酶结合的抑制 C与几种核糖衍生的伽马-内酯一起观察到 通过化合物的模型。 酪氨酸激酶：苯乙烯系列中的结构要求 已经成功地建立了对酪氨酸激酶的抑制和 测试过。 逆转录酶抑制剂：扩环研究 奥昔洛辛已完成。其中一个合成的异构体显示 抗艾滋病毒的活性和另一个没有。这个结果是相容的 使用建模数据。 三维数据库：DTP中大约一半的化合物 数据库已转换为三维结构和一个 开发了基于距离的搜索系统。