In Silico Footprinting of Ligands Binding to the Minor Groove of DNA

The sequence selectivity of small molecules binding to the minor groove of DNA can be predicted by “in silico footprinting”. Any potential ligand can be docked in the minor groove and then moved along it using simple simulation techniques. By applying a simple scoring function to the trajectory afte...

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Bibliographic Details
Published in:Journal of chemical information and modeling 2005-11, Vol.45 (6), p.1896-1907
Main Authors: Anthony, Nahoum G, Huchet, Guillaume, Johnston, Blair F, Parkinson, John A, Suckling, Colin J, Waigh, Roger D, Mackay, Simon P
Format: Article
Language:English
Subjects:
Binding sites
Chemical compounds
Computer Simulation
Crystallography
Crystallography, X-Ray
Deoxyribonucleic acid
DNA
DNA - chemistry
DNA - drug effects
DNA - ultrastructure
DNA Footprinting - methods
Drug Evaluation, Preclinical
Ligands
Magnetic Resonance Spectroscopy
Nucleic Acid Conformation
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Summary:The sequence selectivity of small molecules binding to the minor groove of DNA can be predicted by “in silico footprinting”. Any potential ligand can be docked in the minor groove and then moved along it using simple simulation techniques. By applying a simple scoring function to the trajectory after energy minimization, the preferred binding site can be identified. We show application to all known noncovalent binding modes, namely 1:1 ligand:DNA binding (including hairpin ligands) and 2:1 side-by-side binding, with various DNA base pair sequences and show excellent agreement with experimental results from X-ray crystallography, NMR, and gel-based footprinting.
ISSN:1549-9596
1549-960X
DOI:10.1021/ci050153b