Structural Insight of NICD-MAML Interactions: Virtual Screening, Docking and Molecular Dynamics Study for Identification of Potential Inhibitor

Title:Structural Insight of NICD-MAML Interactions: Virtual Screening, Docking and Molecular Dynamics Study for Identification of Potential Inhibitor

Volume: 13 Issue: 4

Author(s): Noopur Sinha, Saikat Chowdhury and Ram Rup Sarkar

Affiliation:

Keywords: Notch signalling, NICD, MAML, potential inhibitor, free energy of binding, ZINC01690699.

Abstract: Activation of Notch signalling pathway is triggered by binding of NICD to transcription factor CSL and transcriptional co-activator MAML, which involves in various biological functions as well as progression of diseases. Recent prediction shows suppression of cancer causing genes of this pathway through inhibition of NICD-MAML interaction. Through virtual screening against “NCI Diversity 3” of Zinc database, we identified a potential inhibitor “ZINC01690699” (1-N,4-N-bis[3-(1Hbenzimidazol- 2-yl)phenyl]benzene-1,4-dicarboxamide; 1-N,4-dicarboxamide) possessing highest binding affinity to block the two distinct Binding Sites of NICD to inhibit NICD-MAML interaction and also found the most imperative and essential Binding Site (Site I). Inhibition of this interaction caused by binding of ZINC01690699 is validated by protein-protein docking and the prolonged binding as well as stability of NICD-Inhibitor complex is supported by molecular dynamics simulation. The study not only identifies the best inhibitor but also proposes a potential drug for the treatment of cancers.

Cite this article as:

Sinha Noopur, Chowdhury Saikat and Sarkar Rup Ram, Structural Insight of NICD-MAML Interactions: Virtual Screening, Docking and Molecular Dynamics Study for Identification of Potential Inhibitor, Letters in Drug Design & Discovery 2016; 13 (4) . https://dx.doi.org/10.2174/1570180812666150819003634