title: Sequence-specific positions of water molecules at the interface between DNA and minor groove binders.
abstract: Ligands able to specifically recognize DNA sequences are of fundamental interest as transcription-controlling drugs. Herein, we analyze the positions of water molecules relative to B-DNA base pairs in the minor groove of X-ray and NMR protein data bank (PDB) structures. The patterns observed for water molecules at the interface between DNA and a ligand are compared with those obtained for structures without a ligand. Although the ligand end groups are often charged, and therefore highly hydrated, they do not alter the water patterns, which show considerable differences for the AT and CG base pairs. For AT they are much more precise than for CG in both ligand-containing and ligand-free structures. This behavior strongly indicates that the release of water molecules upon ligand binding leads to a gain of entropy and explains why this effect is especially pronounced for A-tract B-DNA sequences.
authors.affiliation: Institute of General, Inorganic and Theoretical Chemistry, University of Innsbruck, Innrain 52a, A-6020 Innsbruck, Austria. Gudrun.Spitzer@uibk.ac.at
authors.forename: Gudrun M
authors.initials: GM
authors.lastname: Spitzer
authors.forename: Julian E
authors.initials: JE
authors.lastname: Fuchs
authors.forename: Patrick
authors.initials: P
authors.lastname: Markt
authors.forename: Johannes
authors.initials: J
authors.lastname: Kirchmair
authors.forename: Bernd
authors.initials: B
authors.lastname: Wellenzohn
authors.forename: Thierry
authors.initials: T
authors.lastname: Langer
authors.forename: Klaus R
authors.initials: KR
authors.lastname: Liedl
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D019277:Entropy; D008024:Ligands; D014867:Water / Q000737:chemistry*
chemical_list: D008024:Ligands; D014867:Water; D004247:DNA