title: Evidence of colorectal cancer risk associated variant Lys25Ser in the proximity of human bone morphogenetic protein 2.
abstract: Colorectal cancer (CRC) is the third most prevalent cancer and fourth leading cause of cancer-related deaths globally. It has been shown that the nsSNP variants play an important role in diseases, however it remained unclear how these variants are associated with the disease. Recently, several CRC risk associated SNPs have been discovered, however rs961253 (Lys25Arg at 20p12.3) located in the proximity of bone morphogenetic protein 2 (Bmp2) and fermitin family homolog 1 Fermt1 genes have been reported to be highly associated with the CRC risk. Here we provide evidence for the first time in silico biological functional and structural implications of non-synonymous (nsSNPs) CRC disease-associated variant Lys25Arg via molecular dynamic (MD) simulation. Protein structural analysis was performed with a particular variant allele (A/C, Lys25Arg) and compared with the predicted native protein structure. Our results showed that this nsSNP will cause changes in the protein structure and as a result is associated with the disease. In addition to the native and mutant 3D structures of CRC associated risk allele protein domain (CRAPD), they were also analyzed using solvent accessibility models for further protein stability confirmation. Taken together, this study confirmed that this variant has functional effect and structural impact on the CRAPD and may play an important role in CRC disease progression; hence it could be a reasonable approach for studying the effect of other deleterious variants in future studies.
authors.affiliation: Genome Research Chair Unit, Department of Biochemistry, College of Science, King Saud University, P. O. Box 2455, Riyadh 11541, Saudi Arabia.
authors.forename: Wajahatullah
authors.initials: W
authors.lastname: Khan
authors.forename: Zainularifeen
authors.initials: Z
authors.lastname: Abduljaleel
authors.forename: Mohammed
authors.initials: M
authors.lastname: Alanazi
authors.forename: Mohamed
authors.initials: M
authors.lastname: Elrobh
mesh_terms: D000483:Alleles; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D056004:Molecular Dynamics Simulation; D020641:Polymorphism, Single Nucleotide; D011487:Protein Conformation
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2