title: Efficient calculation of many stacking and pairing free energies in DNA from a few molecular dynamics simulations.
abstract: Through the use of the one-step perturbation approach, 130 free energies of base stacking and 1024 free energies of base pairing in DNA have been calculated from only five simulations of a nonphysical reference state. From analysis of a diverse set of 23 natural and unnatural bases, it appears that stacking free energies and stacking conformations play an important role in pairing of DNA nucleotides. On the one hand, favourable pairing free energies were found for bases that do not have the possibility to form canonical hydrogen bonds, while on the other hand, good hydrogen-bonding possibilities do not guarantee a favourable pairing free energy if the stacking of the bases dictates an unfavourable conformation. In this application, the one-step perturbation approach yields a wealth of both energetic and structural information at minimal computational cost.
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, ETH-Hönggerberg, 8093 Zurich, Switzerland.
authors.forename: Chris
authors.initials: C
authors.lastname: Oostenbrink
authors.forename: Wilfred F
authors.initials: WF
authors.lastname: van Gunsteren
mesh_terms: D020029:Base Pairing; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D004261:DNA Replication; D006860:Hydrogen Bonding
chemical_list: D004247:DNA