Structural dynamics and quantum mechanical aspects of shikonin derivatives as CREBBP bromodomain inhibitors

Journal of Molecular Graphics & Modelling
Sarmistha Mitra, Raju Dash

Abstract

The Proteins involved in the chemical modification of lysine residues in histone, is currently being excessively focused as the therapeutic target for the treatment of cell related diseases like cancer. Among these proteins, the epigenetic reader, CREB-binding protein (CREBBP) bromodomain is one of the most prominent targets for effective anticancer drug design, which is responsible for the reorganization of acetylated histone lysine residues. Therefore, this study employed an integrative approach of structure based drug design, in combination with Molecular Dynamics (MD) and QM/MM study to identify as well as to describe the binding mechanism of two shikonin derivatives, acetylshikonin and propionylshikonin as inhibitors of CREBBP bromodomain. Here induced fit docking strategy was employed to explore the important intrinsic interactions of ligands with CREBBP bromodomain, consistently molecular dynamics simulation with two different methods and binding energy calculations by MM-GBSA and MM-PBSA were adopted to determine the stability of intermolecular interactions between protein and ligands. The results showed that both these derivatives made direct contacts with the important conserved residues of the active site, where prop...Continue Reading

Citations

May 28, 2019·Current Pharmaceutical Design·Raju DashS M Zahid Hosen
Oct 15, 2019·Journal of Biomolecular Structure & Dynamics·Shafi MahmudN Absar
Jun 14, 2020·International Journal of Molecular Sciences·Balázs Zoltán Zsidó, Csaba Hetényi
Oct 13, 2020·European Journal of Medicinal Chemistry·Zhang-Xu HeWen Zhao
Nov 17, 2020·Computational Biology and Chemistry·Yeasmin Akter MunniRaju Dash
Dec 31, 2020·International Journal of Molecular Sciences·Md Ariful IslamIl Soo Moon

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