期刊
JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
卷 -, 期 -, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/07391102.2022.2154849
关键词
Protein tyrosine kinase Lyn; phytoconstituents; drug discovery; molecular docking; virtual screening; molecular dynamics simulations
资金
- Indian Council of Medical Research, Government of India [ISRM/12(22)/2020]
Tyrosine-protein kinase Lyn (LynK) has been identified as a promising therapeutic target for cancer and diabetes. In this study, the researchers used a virtual screening process to discover two natural compounds, Glabrene and Lactupicrin, with high affinity and specificity for LynK. These compounds interact with the ATP-binding pocket of LynK and exhibit drug-like properties, as demonstrated by molecular dynamics simulation.
Tyrosine-protein kinase Lyn (LynK) has emerged as one of the most attractive therapeutic targets for cancer and diabetes. In this study, we used a multistep virtual screening process of natural compounds to discover potential inhibitors of LynK from the IMPPAT database. The primary filters were based on Lipinski rules, ADMET properties, and PAINS patterns. Then, binding affinities and interaction analyses were carried out for the high-affinity selectivity of the compounds towards LynK. Eventually, two natural compounds, Glabrene and Lactupicrin, were identified with high affinity and specificity for the LynK-binding pocket. Both compounds exhibited drug-like properties, as predicted by ADMET analysis and physicochemical parameters. The molecular dynamics (MD) simulation study revealed that these compounds bind to the ATP-binding pocket of LynK and interact with functionally significant residues with stability without inducing any significant structural changes to the protein. Ultimately, the identified compounds may be regarded as promising LynK inhibitors and can be used as lead molecules in the drug development against LynK-related diseases.Communicated by Ramaswamy H. Sarma
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据