Deciphering the crucial residues involved in heterodimerization of Bak peptide and anti-apoptotic proteins for apoptosis

Journal of Biomolecular Structure & Dynamics
Parthiban Marimuthu, Kalaimathy Singaravelu

Abstract

B-cell lymphoma 2 (Bcl-2) family proteins are the central regulators of apoptosis, functioning via mitochondrial outer membrane permeabilization. The family members are involved in several stages of apoptosis regulation. The overexpression of the anti-apoptotic proteins leads to several cancer pathological conditions. This overexpression is modulated or inhibited by heterodimerization of pro-apoptotic BH3 domain or BH3-only peptides to the hydrophobic groove present at the surface of anti-apoptotic proteins. Additionally, the heterodimerization displayed differences in binding affinity profile among the pro-apoptotic peptides binding to anti-apoptotic proteins. In light of discovering the novel peptide/drug molecules that contain the potential to inhibit specific anti-apoptotic protein, it is necessary to understand the molecular basis of recognition between the protein and its binding partner (peptide or ligand) along with its binding energies. Therefore, the present work focused on deciphering the molecular basis of recognition between pro-apoptotic Bak peptide binding to different anti-apoptotic (Bcl-xL, Bfl-1, Bcl-W, Mcl-1, and Bcl-2) proteins using advanced Molecular Dynamics (MD) approach such as Molecular Mechanics-Gener...Continue Reading

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Citations

Aug 11, 2017·Journal of Biomolecular Structure & Dynamics·Parthiban MarimuthuKalaimathy Singaravelu
May 11, 2018·Journal of Biomolecular Structure & Dynamics·Parthiban Marimuthu, Kalaimathy Singaravelu

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Datasets Mentioned

BETA
AA1268

Methods Mentioned

BETA
X-ray

Software Mentioned

Maestro
sander
AMBER
MMPBSA
SASA
QHA
Ambertools
NAMD
NMA
py

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