Molecular interaction analysis of cigarette smoke carcinogens NNK and NNAL with enzymes involved in DNA repair pathways: An in silico approach

DNA damage occurs almost all the times in cells, but is repaired also continuously. Occurrence of all these mutations and theiraccumulation in one cell which finally becomes tumorigenic/carcinogenic appears possible if the DNA repair mechanism ishampered. We hypothesize that alterations in DNA repair pathways, either all or at least at one i.e. genetic, translational or posttranslationallevel, becomes quite imperative for the initiation and progression of Cancer. Therefore, we investigated the interactioncapability of some carcinogens with the enzymes involved in the DNA repair mechanisms. Cigarette smoke''s derivatives likeNNK and NNAL are well established carcinogens. Hence, we analyzed 72 enzymes involved in the DNA repair Mechanisms fortheir interactions with ligands (NNK and NNAL). The binding efficiencies with enzymes ranging from +36.96 to -7.47 Kcal/Mol.Crystal Structure of Human Carbonmonoxy-Haemoglobin at 1.25 Å Resolution, PDB ID-1IRD as a +Ve control, showedbinding energy -6.31 to -6.68 Kcal/Mol. and Human heat shock factor-binding protein 1, PDB ID- 3CI9 as a -Ve control, showed -3.91 to +2.09 Kcal/Mol. Binding was characterized for the enzymes sharing equivalent or better interaction as compared to +Vecontrol. Study indicated the loss of functions of these enzymes, which probably could be a reason for fettering of DNA repairpathways resulting in damage accumulation and finally cancer formation.