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

N.G. Anthony, G. Huchet, B.F. Johnston, B.F. Parkinson, C.J. Suckling, R.D. Waigh, S.P. Mackay

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1896-1907
Number of pages11
JournalJournal of Chemical Information and Modeling
Volume45
Issue number6
DOIs
Publication statusPublished - 5 Oct 2005

Fingerprint

DNA
Ligands
energy
simulation
X ray crystallography
Binding sites
Gels
Binding Sites
Trajectories
Nuclear magnetic resonance
Molecules

Keywords

  • Silico Footprinting
  • Ligands Binding
  • Minor Groove
  • DNA
  • energy minimization
  • noncovalent binding modes
  • X-ray crystallography

Cite this

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abstract = "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.",
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In Silico Footprinting of Ligands Binding to the Minor Groove of DNA. / Anthony, N.G.; Huchet, G.; Johnston, B.F.; Parkinson, B.F.; Suckling, C.J.; Waigh, R.D.; Mackay, S.P.

In: Journal of Chemical Information and Modeling, Vol. 45, No. 6, 05.10.2005, p. 1896-1907.

Research output: Contribution to journalArticle

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T1 - In Silico Footprinting of Ligands Binding to the Minor Groove of DNA

AU - Anthony, N.G.

AU - Huchet, G.

AU - Johnston, B.F.

AU - Parkinson, B.F.

AU - Suckling, C.J.

AU - Waigh, R.D.

AU - Mackay, S.P.

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AB - 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.

KW - Silico Footprinting

KW - Ligands Binding

KW - Minor Groove

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KW - energy minimization

KW - noncovalent binding modes

KW - X-ray crystallography

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