title: A new insight into structural and functional impact of single-nucleotide polymorphisms in PTEN gene.
abstract: Phosphatase and tensin homolog (PTEN) plays essential roles in cellular processes including survival, proliferation, energy metabolism, and cellular architecture. Activating the mutations of PTEN has long been known to produce a variety of disorders, mainly diabetes and cancer in humans. Owing to the importance of PTEN gene, a functional analysis using different in silico approaches was undertaken to explore the possible associations between genetic mutations and phenotypic variation. SIFT, PolyPhen, I-Mutant 3.0, SNP&GO, and PHD-SNP were used for initial screening of functional nsSNPs. From the observed results, three mutations R47G, H61D, and V343E were selected based on their surface accessibility and total energy change. By molecular dynamics approach, H61D showed increase in flexibility, radius of gyration, solvent accessibility, and deviated more from the native structure which was supported by the decrease in the number of hydrogen bonds. Further from principal component analysis and interaction analysis, we identified significant structural changes that can reasonably explain the involvement of deviations in stability caused by mutations. Our analysis also predicts the involvement of SNPs that could potentially influence post-translational modifications in PTEN gene. These in silico predictions could provide a new insight into structural and functional impact of PTEN polymorphisms.
authors.affiliation: Centre for Nanobiotechnology, Medical Biotechnology Division, School of Biosciences and Technology, Vellore, India. georgecp77@yahoo.co.in
authors.forename: C
authors.initials: C
authors.lastname: George Priya Doss
authors.forename: B
authors.initials: B
authors.lastname: Rajith
mesh_terms: D000595:Amino Acid Sequence; D016208:Databases, Factual; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D051059:PTEN Phosphohydrolase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D060066:Protein Interaction Maps; D013816:Thermodynamics
chemical_list: D051059:PTEN Phosphohydrolase