Exploring the effect of aplidin on low molecular weight protein tyrosine phosphatase by molecular docking and molecular dynamic simulation study.

• 影响指数: 3.737
• 发表时间: Dec 2019
• 来源期刊: Comput Biol Chem
• DOI: 10.1016/j.compbiolchem.2019.107123
• PMID: 31561070
• 文章类型: Journal Article
• 中科院分区: Q3
• 方向: 综合性期刊
• 作者列表: Sun YZ,Wu JW,Lu XH,Ma Y,Wang RL

关键词: Cancer; LMW-PTP; Molecular docking; Molecular dynamics simulation; Post-dynamics analyses

Mesh: Catalytic Domain / drug effects; Depsipeptides / chemistry pharmacology; Enzyme Inhibitors / chemistry pharmacology; Humans; Molecular Conformation; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Weight; Peptides, Cyclic; Protein Tyrosine Phosphatases / antagonists & inhibitors chemistry metabolism

Abstract

The low molecular weight protein tyrosine phosphatase (LMW-PTP) could regulate many signaling pathways, and it had drawn attention as a potential target for cancer. As previous report has indicated that the aplidin could inhibit the LMW-PTP, and thus, the relevant cancer caused by the abnormal regulation of the LMW-PTP could be remission. However, the molecular mechanism of inhibition of the LMW-PTP by the aplidin had not been fully understood. In this study, various computational approaches, namely molecular docking, MDs and post-dynamic analyses were utilized to explore the effect of the aplidin on the LMW-PTP. The results suggested that the intramolecular interactions of the residues in the two sides of the active site (Ser43-Ala55 and Pro121-Asn134) and the P-loop region (Leu13-Ser19) in the LMW-PTP was disturbed owing to the aplidin, meanwhile, the π-π interaction between Tyr131 and Tyr132 might be broken. The Asn15 might be the key residue to break the residues interactions. In a word, this study may provide more information for understanding the effect of inhibition of the aplidin on the LMW-PTP.