Evidence of Colorectal Cancer-Associated Mutation in MCAK: A Computational Report

• DOI: 10.1007/s12013-013-9572-1
• Publication Date: 2013-04-05T06:40:03Z
• Authors: Ambuj Kumar; Vidya Rajendran; Rao Sethumadhavan; Rituraj Purohit
• Keywords: Principal Component Analysis; 0303 health sciences; Binding Sites; Kinesins; Hydrogen Bonding; Ligands; Polymorphism, Single Nucleotide; Protein Structure, Tertiary; 3. Good health; Molecular Docking Simulation; 03 medical and health sciences; Adenosine Triphosphate; Phenotype; Mutation; Humans; Thermodynamics; Colorectal Neoplasms; Software

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.