An analysis of van der Waals attractive forces in DNA-minor groove binding

Abstract

Force field methodology (AMBER) has been used in conjunction with X-ray crystallographic data to evaluate the importance of attractive van der Waals forces in complexes of d(CGCGAATTCGCG) 2, d(CGCAAATTTGCG) 2, and d(CGCGTTAACGCG) 2 with a variety of ligands. Large negative energies were obtained (−128 to −246 kJ/mol) which, with exception of netropsin, were insensitive to base-pair sequence. In conjunction with X-ray crystallographic data, force field methodology (AMBER) was used to evaluate the relative magnitude of van der Waals attractive forces in d(CGCGAATTCGCG) 2, d(CGCAAATTTGCG) 2 and d(CGCGTTAACGCG) 2 complexes. In every case, large negative attractive energies were obtained (-128 to -246 kJ/mol) which, with exception of netropsin, were insensitive to base-pair sequence. Ligands with several contiguous aromatic rings (e.g., Hoechst 33258) utilize significantly greater van der Waals attractive forces than ligands with aliphatic linkers of CH, O, and/or N atoms (e.g., pentamidine, distamycin).