Hydrogen-Bonding Patterns of Minor Groove-Binder−DNA Complexes Reveal Criteria for Discovery of New Scaffolds

Minor groove-binding ligands are able to control gene expression and are of great interest for therapeutic applications. We extracted hydrogen-bonding geometries from all available structures of minor groove-binder−DNA complexes of two noncovalent binding modes, namely 1:1 (including hairpin and cyc...

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Bibliographic Details
Published inJournal of Chemical Information and Modeling Vol. 49; no. 4; pp. 1063 - 1069
Main Authors Spitzer, Gudrun M, Wellenzohn, Bernd, Markt, Patrick, Kirchmair, Johannes, Langer, Thierry, Liedl, Klaus R
Format Journal Article
LanguageEnglish
Published United States American Chemical Society 27.04.2009
Subjects
Base Pairing
Binding sites
Databases, Genetic
Deoxyribonucleic acid
DNA
DNA - chemistry
Gene expression
Gene Expression - drug effects
Hydrogen Bonding
Hydrogen bonds
Ligands
Nucleic Acid Conformation
Pharmaceutical Modeling
Software
Water - chemistry
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Summary:Minor groove-binding ligands are able to control gene expression and are of great interest for therapeutic applications. We extracted hydrogen-bonding geometries from all available structures of minor groove-binder−DNA complexes of two noncovalent binding modes, namely 1:1 (including hairpin and cyclic ligands) and 2:1 ligand/DNA binding. Positions of the ligand atoms involved in hydrogen bonding deviate from idealized hydrogen bond geometries and do not exploit the possibilities indicated by water molecules. Therefore, we suggest the inclusion of shape-based descriptors rather than hydrogen-bond patterns in virtual screening protocols for the identification of innovative minor groove-binding scaffolds.
ISSN:1549-9596
1520-5142
1549-960X
DOI:10.1021/ci800455f