title: Complex disruption effect of natural polyphenols on Bcl-2-Bax: molecular dynamics simulation and essential dynamics study.
abstract: Apoptosis (programmed cell death) is a process by which cells died after completing physiological function or after a severe genetic damage. Apoptosis is mainly regulated by the Bcl-2 family of proteins. Anti apoptotic protein Bcl-2 prevents the Bax activation/oligomerization to form heterodimer which is responsible for release of the cytochrome c from mitochondria to the cytosol in response to death signal. Quercetin and taxifolin (natural polyphenols) efficiently bound to hydrophobic groove of Bcl-2 and altered the structure by inducing conformational changes. Taxifolin was found more efficient when compared to quercetin in terms of interaction energy and collapse of hydrophobic groove. Taxifolin and quercetin were found to dissociate the Bcl-2-Bax complex during 12 ns MD simulation. The effect of taxifolin and quercetin was, further validated by the MD simulation of ligand-unbound Bcl-2-Bax which showed stability during the simulation. Obatoclax (an inhibitor of Bcl-2) had no significant dissociation effect on Bcl-2-Bax during simulation which favored the previous experimental results and disruption effect of taxifolin and quercetin.
authors.affiliation: a School of Biochemical Engineering , Indian Institute of Technology (Banaras Hindu University) , Varanasi 221005 , India.
authors.forename: Sharad
authors.initials: S
authors.lastname: Verma
authors.forename: Amit
authors.initials: A
authors.lastname: Singh
authors.forename: Abha
authors.initials: A
authors.lastname: Mishra
mesh_terms: D000465:Algorithms; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007211:Indoles; D007700:Kinetics; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D059808:Polyphenols / Q000737:chemistry* / Q000378:metabolism; D025341:Principal Component Analysis; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry* / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000737:chemistry* / Q000378:metabolism
chemical_list: D007211:Indoles; D046912:Multiprotein Complexes; D059808:Polyphenols; D019253:Proto-Oncogene Proteins c-bcl-2; D011758:Pyrroles; D051028:bcl-2-Associated X Protein; D011794:Quercetin; C003377:taxifolin; C520962:obatoclax
keywords: Bcl-2-Bax complex; molecular dynamics simulation; obatoclax; quercetin; taxifolin