中南民族大学学报（自然科学版）2023，Vol.42Issue(2)：150-156,7.DOI:10.20056/j.cnki.ZNMDZK.20230202
磷酸二酯酶4B专一性抑制剂设计中的构象分析
Conformation analysis in the design of phosphodiesterase 4B selectivity inhibitors
摘要
Abstract
In order to investigate the structure-activity relationship of phosphodiesterase 4 (PDE4) inhibitors Y3, Y8 and A33 and find out why Y3 and Y8 demonstrated weak inhibitory activity, molecular docking, conformation search, quantum mechanical calculations, molecular dynamic, and molecular mechanics energies combined with the generalized Born and surface area continuum solvation (MM-GBSA) calculations were performed. The results showed that Y3, Y8 and A33 had similar binding modes and binding affinities with PDE4 subtypes PDE4B and PDE4D. However, the binding conformations for Y3 and Y8 in PDE4B/PDE4D and the conformation for A33 in PDE4D were of high-energy, whereas the conformation for A33 in PDE4B was of low-energy. Hence, the high internal energies of the binding conformations were the main factor that led to weak inhibitory activities of these ligands. The conformation analysis was vitally important in drug design.关键词
吡啶衍生物/对接/亲和能/构象分析/药物设计Key words
pyridine derivatives/docking/binding affinity/conformation analysis/drug design分类
化学化工引用本文复制引用
李琳慧,李欣,王小宁,赵新筠,陈喜,湛昌国..磷酸二酯酶4B专一性抑制剂设计中的构象分析[J].中南民族大学学报（自然科学版）,2023,42(2):150-156,7.基金项目
国家自然科学基金资助项目(21273089) （21273089）
中央高校基本科研业务费专项资金资助项目(CZY20020) （CZY20020）
