title: Molecular Dynamics Simulations of 5-Hydroxycytosine Damaged DNA.
abstract: Oxidation of cytosine is a leading cause of mutations and can lead to cancer. Here we report molecular dynamics simulations that characterized the structure and flexibility of 5-hydroxycytosine damaged DNA. A total of four systems were studied: undamaged DNA, damaged DNA base paired to a matching guanine, damaged DNA base paired to a mismatching adenine, and the corresponding undamaged mismatched strand. The simulations showed high spatial similarity between undamaged and damaged DNA; however, the matched damaged strand had greater overtwisting flexibility, and for both the matched and unmatched strands sugar puckering was much more flexible at the damaged site. The mismatch introduced larger changes, notably a loss in hydrogen bonding and a gain in stacking interactions, as well as effects on base pair and step geometry and solvation. Implications for damage recognition are discussed.
authors.affiliation: Department of Chemistry, University of South Florida , 4202 East Fowler Avenue CHE 205, Tampa, Florida 33620, United States.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Karolak
authors.affiliation: Department of Chemistry, University of South Florida , 4202 East Fowler Avenue CHE 205, Tampa, Florida 33620, United States.
authors.forename: Arjan
authors.initials: A
authors.lastname: van der Vaart
mesh_terms: D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D004249:DNA Damage; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D010084:Oxidation-Reduction
chemical_list: C017400:5-hydroxycytosine; D003596:Cytosine; D004247:DNA