title: Cisplatin cytotoxicity: a theoretical study of induced mutations.
abstract: We investigate possible mutations in the genetic code induced by cisplatin with an approach combining molecular dynamics (MD) and hybrid quantum mechanics/molecular mechanics (QM/MM) calculations. Specifically, the impact of platination on the natural tautomeric equilibrium in guanine-cytosine (GC) base pairs is assessed to disclose the possible role played by non-canonical forms in anti-tumour activity. To obtain valuable predictions, the main interactions present in a real DNA environment, namely hydration and stacking, are simultaneously taken into account. According to our results, the Pt-DNA adduct promotes a single proton transfer reaction in GC in the DNA sequence AG[combining low line]G[combining low line]C. Such rare tautomers might play an important role in the cisplatin biological activity since they meet the stability requirements necessary to promote a permanent mutation.
authors.affiliation: CEISAM, UMR CNRS 6230, BP 92208, Université de Nantes, 2, Rue de la Houssinière, 44322 Nantes, Cedex 3, France.
authors.forename: José P
authors.initials: JP
authors.lastname: Cerón-Carrasco
authors.forename: Denis
authors.initials: D
authors.lastname: Jacquemin
authors.forename: Emilie
authors.initials: E
authors.lastname: Cauët
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D002945:Cisplatin / Q000633:toxicity*; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D018736:DNA Adducts / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D016296:Mutagenesis / Q000187:drug effects*; D009154:Mutation / Q000187:drug effects*; D011789:Quantum Theory
chemical_list: D000970:Antineoplastic Agents; D018736:DNA Adducts; D004247:DNA; D002945:Cisplatin