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

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. Abstract 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).