Evidence of colorectal cancer-associated mutation in MCAK: a computational report.

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.

Contribution of unconventional C-H...O bonds to the structural stability of antimicrobial peptides.

The native structure of Antimicrobial peptides is stabilized by a large number of individually weak forces; a complete understanding of folding implies the need to evaluate the contribution of each of these, including nonconventional hydrogen bonds. In this work, we have analyzed the influence of C-H...O interactions in the structural stability of Antimicrobial peptides by comparison with conventional hydrogen bond. There are a number of amino acid residues that can form hydrogen bonds via their side chains in addition to their peptide group. Perhaps highest contribution in this category is polar residue (Cys) and charged residues such as Lys and Arg. A total of 2513 C-H...O interactions were found in a data set of 53 Antimicrobial peptides. Among the 2513 nonconventional interactions observed in the data set, 40% of interactions are bonded to alpha carbon. This is consistent with the fact that the hydrogens are more acidic than others. Most prominent were side-chain to main-chain C-H...O interactions (SM-C-H...O). 92% of the stabilizing centers in the Antimicrobial peptides were found to be involved in C-H...O interactions. These interactions are mainly formed by short range contacts. Moreover, the study shows that, there is an average of more than one C-H...O interactions observed for every single residue in the Antimicrobial peptides data set. It is concluded that the C-H...O interaction can, indeed, be categorized as a true stabilizing force like hydrogen bond in Antimicrobial peptides.