Browsing by Author "Dakal, Tikam Chand"

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    Mechanistic basis of antimicrobial actions of silver nanoparticles
    (Frontiers in Microbiology, 2016) Dakal, Tikam Chand; Kumar, Anu; Majumdar, Rita.S; Yadav, Vinod
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    Predicting the functional consequences of non-synonymous single nucleotide polymorphisms in IL8 gene
    (Scientific Reports, 2017) Dakal, Tikam Chand; Kala, Deepak; Dhiman, Gourav; Yadav, Vinod; Krokhotin, Andrey
    Here we report an in-silico approach for identification, characterization and validation of deleterious non-synonymous SNPs (nsSNPs) in the interleukin-8 gene using three steps. In first step, sequence homology-based genetic analysis of a set of 50 coding SNPs associated with 41 rsIDs using SIFT (Sorting Intolerant from Tolerant) and PROVEAN (Protein Variation Effect Analyzer) identified 23 nsSNPs to be putatively damaging/deleterious in at least one of the two tools used. Subsequently, structurehomology based PolyPhen-2 (Polymorphism Phenotyping) analysis predicted 9 of 23 nsSNPs (K4T, E31A, E31K, S41Y, I55N, P59L, P59S, L70P and V88D) to be damaging. According to the conditional hypothesis for the study, only nsSNPs that score damaging/deleterious prediction in both sequence and structural homology-based approach will be considered as ‘high-confidence’ nsSNPs. In step 2, based on conservation of amino acid residues, stability analysis, structural superimposition, RSMD and docking analysis, the possible structural-functional relationship was ascertained for high-confidence nsSNPs. Finally, in a separate analysis (step 3), the IL-8 deregulation has also appeared to be an important prognostic marker for detection of patients with gastric and lung cancer. This study, for the first time, provided in-depth insights on the effects of amino acid substitutions on IL-8 protein structure, function and disease association.