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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.

SUBMITTER: Wittayanarakul K

PROVIDER: S-EPMC4007966 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Ranking ligand affinity for the DNA minor groove by experiment and simulation.

Wittayanarakul Kitiyaporn K Anthony Nahoum G NG Treesuwan Witcha W Hannongbua Supa S Alniss Hasan H Khalaf Abedawn I AI Suckling Colin J CJ Parkinson John A JA Mackay Simon P SP

ACS medicinal chemistry letters 20100730 8

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 th ...[more]

PMID: 24900221

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