Computational Biology and Chemistry .
Volume 83, December 2019 .
Highlights :
The study of the mechanism of molecular basis of the ligand-aplidin inhibition of the LMW-PTP for the first time.
The study was to reveal the interactions of ligand with residues in the active site of LMW-PTP by MD simulations.
The Asn 15 was first found as the key residue, which plays an important role in disturbing the residue interactions.
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.
Graphical abstract
The changes of the interactions of the key residues (Asn15) between theLMW-PTP and LMW-PTP/aplidin systems.
