Open AccessComputational and structural based approach to identify malignant nonsynonymous single nucleotide polymorphisms associated with CDK4 gene
Author(s) -
Rahatul Islam,
Md. Mashiur Rahaman,
Hammadul Hoque,
Nahid Hasan,
Shamsul H. Prodhan,
Asfia Ruhama,
Nurnabi Azad Jewel
Publication year - 2021
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0259691
Subject(s) - nonsynonymous substitution , missense mutation , single nucleotide polymorphism , biology , dbsnp , genetics , mutation , cancer research , silent mutation , gene , genotype , genome
Cycline-dependent kinase 4 (CDK4), an enzyme of the cycline dependent or Ser/Thr protein kinase family, plays a role in cell cycle progression (G1 phase) by phosphorylating a tumor suppressor protein called pRB. Alteration of this enzyme due to missense mutation/ nonsynonymous single nucleotide polymorphisms (nsSNPs) are responsible for various types of cancer progression, e.g. melanoma, lung cancer, and breast cancer. Hence, this study is designed to identify the malignant missense mutation of CDK4 from the single nucleotide polymorphism database (dbSNP) by incorporating computational algorithms. Out of 239 nsSNPs; G15S, D140Y and D140H were predicted to be highly malignant variants which may have a devastating impact on protein structure or function. We also found defective binding motif of these three mutants with the CDK4 inhibitor ribociclib and ATP. However, by incorporating molecular dynamic simulation, our study concludes that the superiority of G15S than the other two mutants (D140Y and D140H) in destabilizing proteins nature.