title: Evidence of colorectal cancer-associated mutation in MCAK: a computational report.
abstract: Computational prediction of disease-associated non-synonymous polymorphism (nsSNP) has provided a significant platform to filter out the pathological mutations from large pool of SNP datasets at a very low cost input. Several methodologies and complementary protocols have been previously implemented and has provided significant prediction results. Although the previously implicated prediction methods were capable of investigating the most likely deleterious nsSNPs, but due to the lack of genotype-phenotype association analysis, the prediction results lacked in accuracy level. In this work we implemented the computational compilation of protein conformational changes as well as the probable disease-associated phenotypic outcomes. Our result suggested E403K mutation in mitotic centromere-associated kinesin protein as highly damaging and showed strong concordance to the previously observed colorectal cancer mutations aggregation tendency and energy value changes. Moreover, the molecular dynamics simulation results showed major loss in conformation and stability of mutant N-terminal kinesin-like domain structure. The result obtained in this study will provide future prospect of computational approaches in determining the SNPs that may affect the native conformation of protein structure and lead to cancer-associated disorders.
authors.affiliation: Bioinformatics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore, 632014, Tamil Nadu, India.
authors.forename: Ambuj
authors.initials: A
authors.lastname: Kumar
authors.forename: Vidya
authors.initials: V
authors.lastname: Rajendran
authors.forename: Rao
authors.initials: R
authors.lastname: Sethumadhavan
authors.forename: Rituraj
authors.initials: R
authors.lastname: Purohit
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D001665:Binding Sites; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006860:Hydrogen Bonding; D016547:Kinesins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D008024:Ligands; D062105:Molecular Docking Simulation; D009154:Mutation; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D017434:Protein Structure, Tertiary; D012984:Software; D013816:Thermodynamics
chemical_list: C091489:KIF2C protein, human; D008024:Ligands; D000255:Adenosine Triphosphate; D016547:Kinesins