High-Risk Non-synonymous SNPs of Human Bcl-2 Gene Alters Structural Stability and Small Molecule Binding
Keywords:Bcl-2 gene, apoptosis, non-synonymous SNPs, HA 14-1
B-cell lymphoma 2 (Bcl-2) gene, which encodes Bcl-2 protein, is vital for apoptotic programmed cell death. In this study, computational approaches were performed to reveal the effect of nonsynonymous single nucleotide polymorphisms (nsSNPs) in Bcl-2 gene. A total of 79 nsSNPs were studied. Amongst all, 11 nsSNPs (M166T, G141E, R129C, S105P, F104S, R98L, L97P, H94P, V93A, G27S, V15L) were located at highly conserved region or functionally important domains with a high probability of being deleterious for Bcl-2 structure or role. Except for H94P, rest of the high-risk nsSNPs displayed decreased stability of BcL-2 structure. However, F104S attracted significant attention because it exhibited considerably reduced binding affinity than wild type Bcl-2 protein against HA 14-1 antagonist. This extensive computational experiment will assist as a valuable data source for upcoming populationbased studies.