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 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.
Anthony
Nahoum G
NG
Department of Pharmaceutical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, Scotland.
Huchet
Guillaume
G
Johnston
Blair F
BF
Parkinson
John A
JA
Suckling
Colin J
CJ
Waigh
Roger D
RD
Mackay
Simon P
SP
D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000187:drug effects* / Q000648:ultrastructure; D018983:DNA Footprinting / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D009690:Nucleic Acid Conformation
D008024:Ligands; D004247:DNA