分子动力学
对接(动物)
化学
虚拟筛选
蛋白激酶A
Janus激酶3
氢键
分子
小分子
激酶
生物化学
分子模型
组合化学
生物物理学
计算化学
生物
体外
有机化学
细胞毒性T细胞
护理部
医学
抗原提呈细胞
作者
Qi‐Di Zhong,Dongmei Li,Jia-Rui Qin,Linjie Guo,Kaihui Zhao
出处
期刊:Current Computer - Aided Drug Design
[Bentham Science]
日期:2023-05-25
卷期号:19
标识
DOI:10.2174/1573409919666230525154120
摘要
JAK3 kinase inhibitor has become an effective means to treat tumors and autoimmune diseases.In this study, molecular docking and molecular dynamics simulation were used to study the theoretical interaction mechanism between 1-phenylimidazolidine-2-one molecules and JAK3 protein.The results of molecular docking showed that the six 1-phenylimidazolidine-2-one derivatives obtained by virtual screening were bound to the ATP pocket of JAK3 kinase, which were competitive inhibitors of ATP, and were mainly bound to the pocket through hydrogen bonding and hydrophobic interaction. Further, MM/GBSA based on molecular dynamics simulation sampling was used to calculate the binding energy between six molecules and the JAK3 kinase protein. Subsequently, the binding energy was decomposed into the contribution of each amino acid residue, of which Leu905, Lys855, Asp967, Leu956, Tyr904, and Val836 were the main energy-contributing residues. Among them, the molecule numbered LCM01415405 can interact with the specific amino acid Arg911 of JAK3 kinase, suggesting that the molecule may be a selective JAK3 kinase inhibitor. The root-mean-square fluctuation (RMSF) of JAK3 kinase pocket residues during molecular dynamics simulation showed that the combination of six new potential small molecule inhibitors with JAK3 kinase could reduce the flexibility of JAK3 kinase pocket residues.These findings reveal the mechanism of 1-phenylimidazolidine-2-one derivatives on JAK3 protein and provide a relatively solid theoretical basis for the development and structural optimization of JAK3 protein inhibitors.
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