Molecular dynamics simulations of xDNA.

xDNA is a modified DNA, which contains natural as well as expanded bases. Expanded bases are generated by the addition of a benzene spacer to the natural bases. A set of AMBER force-field parameters were derived for the expanded bases and the structural dynamics of the xDNA decamer (xT5' G xT A xC xG C xA xG T3').(xA5' C T xG C G xT A xC A3') was explored using a 22 ns molecular dynamics simulation in explicit solvent. During the simulation, the duplex retained its Watson-Crick base-pairing and double helical structure, with deviations from the starting B-form geometry towards A-form; the deviations are mainly in the backbone torsion angles and in the helical parameters. The sugar pucker of the residues were distributed among a variety of modes; C2' endo, C1' exo, O4' endo, C4' exo, C2' exo, and C3' endo. The enhanced stacking interactions on account of the modification in the bases could help to retain the duplex nature of the helix with minor deviations from the ideal geometry. In our simulation, the xDNA showed a reduced minor groove width and an enlarged major groove width in comparison with the NMR structure. Both the grooves are larger than that of standard B-DNA, but major groove width is larger than that of A-DNA with almost equal minor groove width. The enlarged groove widths and the possibility of additional hydration in the grooves makes xDNA a potential molecule for various applications. Copyright (c) 2009 Wiley Periodicals, Inc.