title: Ranking ligand affinity for the DNA minor groove by experiment and simulation.
abstract: The structural and thermodynamic basis for the strength and selectivity of the interactions of minor groove binders (MGBs) with DNA is not fully understood. In 2003, we reported the first example of a thiazole-containing MGB that bound in a phase-shifted pattern that spanned six base pairs rather than the usual four (for tricyclic distamycin-like compounds). Since then, using DNA footprinting, NMR spectroscopy, isothermal titration calorimetry, and molecular dynamics, we have established that the flanking bases around the central four being read by the ligand have subtle effects on recognition. We have investigated the effect of these flanking sequences on binding and the reasons for the differences and established a computational method to rank ligand affinity against varying DNA sequences.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, United Kingdom.
authors.forename: Kitiyaporn
authors.initials: K
authors.lastname: Wittayanarakul
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, United Kingdom.
authors.forename: Nahoum G
authors.initials: NG
authors.lastname: Anthony
authors.affiliation: Chemistry Department and Center of Nanotechnology, Kasetsart University, Bangkok 10900, Thailand.
authors.forename: Witcha
authors.initials: W
authors.lastname: Treesuwan
authors.affiliation: Chemistry Department and Center of Nanotechnology, Kasetsart University, Bangkok 10900, Thailand.
authors.forename: Supa
authors.initials: S
authors.lastname: Hannongbua
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, United Kingdom.
authors.forename: Hasan
authors.initials: H
authors.lastname: Alniss
authors.affiliation: WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.
authors.forename: Abedawn I
authors.initials: AI
authors.lastname: Khalaf
authors.affiliation: WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.
authors.forename: Colin J
authors.initials: CJ
authors.lastname: Suckling
authors.affiliation: WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, 295 Cathedral Street, Glasgow G1 1XL, United Kingdom.
authors.forename: John A
authors.initials: JA
authors.lastname: Parkinson
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow G4 0NR, United Kingdom.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Mackay
keywords: DNA footprinting; DNA minor groove; Ligand affinity; NMR spectroscopy; isothermal titration calorimetry; minor groove binders; molecular dynamics