title: The N6-methyl group of adenine further increases the BI stability of DNA compared to C5-methyl groups.
abstract: Methylated DNA bases are natural modifications which play an important role in protein-DNA interactions. Recent experimental and theoretical results have shown an influence of the base modification on the conformational behavior of the DNA backbone. MD simulations of four different B-DNA dodecamers (d(GC)(6), d(AT)(6), d(G(5mCG)(5)C), and d(A(T6mA)(5)T)) have been performed with the aim to examine the influence of methyl groups on the B-DNA backbone behavior. An additional control simulation of d(AU)(6) has also been performed to examine the further influence of the C5-methyl group in thymine. Methyl groups in the major groove (as in C5-methylcytosine, thymine, or N6-methyladenine) decrease the BII substate population of RpY steps. Due to methylation a clearer distinction of the BI substate stability between YpR and RpY (CpG/GpC or TpA/ApT) steps arises. A positive correlation between the BII substate population and base stacking distances is seen only for poly(GC). A methyl group added into the major groove increases mean water residence times around the purine N7 atom, which may stabilize the BI substate by improving the hydration network between the DNA backbone and the major groove. The N6-methyl group also forms a water molecule bridge between the N6 and O4 atoms, and thus further stabilizes the BI substate.
authors.affiliation: Institute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria.
authors.forename: Fajar R
authors.initials: FR
authors.lastname: Wibowo
authors.forename: Michael
authors.initials: M
authors.lastname: Trieb
authors.forename: Christine
authors.initials: C
authors.lastname: Rauch
authors.forename: Bernd
authors.initials: B
authors.lastname: Wellenzohn
authors.forename: Klaus R
authors.initials: KR
authors.lastname: Liedl
mesh_terms: D000225:Adenine / Q000737:chemistry*; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D004247:DNA; D000225:Adenine