Correlation Engine 2.0
Clear Search sequence regions

Sizes of these terms reflect their relevance to your search.

Gall bladder cancer (GBC) is the most common malignancy of biliary tract cancer associated with high mortality rate and poor prognosis due to lack of suitable biomarkers. In this study, we explored the structural and functional effects of different missense mutations occurs in SMAD4 that was associated with the development of GBC. We utilized in silico methods to predict the harmful effects of nonsynonymous missense mutations and monitored the stability of protein. We found that all mutations (D351N, G352E, R361C, R361H, E526Q) associated with SMAD4 were deleterious in nature resulting in the formation of deformed or unstable protein structure. Molecular dynamics simulation studies revealed how these mutations affect protein stability, structure, conformation and function. We observed, different mutants increase the compactness and rigidity of SMAD4 protein, alter secondary structure composition, decrease the surface area and protein-ligand interaction and affect its conformation. Findings of current work indicated that the analyzed mutations might affect the structure of protein and its caliber to interact with other molecules, which probably related to functional impairment of SMAD4 upon D351N, G352E, R361C, R361H, E526Q mutations and their involvement in cancer. Hence, the present study has significance of rational drug design and further increase our understanding of GBC development.Communicated by Ramaswamy H. Sarma.


Rakesh Kumar, Rahul Kumar, Pranay Tanwar, G K Rath, Ritesh Kumar, Sunil Kumar, Nihar Dash, Prasenjit Das, Showket Hussain. Deciphering the impact of missense mutations on structure and dynamics of SMAD4 protein involved in pathogenesis of gall bladder cancer. Journal of biomolecular structure & dynamics. 2021 Apr;39(6):1940-1954

Expand section icon Mesh Tags

Expand section icon Substances

PMID: 32151199

View Full Text