Theoretical Study of Sequence Selectivity and Preferred Binding Mode of Psoralen with DNA
Psoralen interaction with two models of DNA was investigated using molecular mechanics and molecular dynamics methods. Calculated energies of minor groove binding and intercalation were compared in order to define a preferred binding mode for the ligand.We found that both binding modes are possible, explaining the low efficiency for mono adduct formation from intercalated ligands. A comparison between the interaction energy for intercalation between different base pairs suggests that the observed sequence selectivity is due to favorable intercalation in 5′-TpA in (AT)n sequences.
Patricia Saenz-Méndez12, Rita C. Guedes3, Daniel J. V. A. dos Santos3, and Leif A. Eriksson1
1 Department of Natural Sciences and Örebro Life Science Center, Örebro University, Örebro 701 82, Sweden
2 Faculty of Chemistry, University of Uruguay (UdelaR), Montevideo 11800, Uruguay
3 Faculty of Pharmacy, University of Lisbon, a. Prof. Gama Pinto Avenue, Lisbon 1649-019, Portugal