Abstract

A molecular mechanics and molecular dynamics approach has been used to examine the structure of the complex formed between pentamidine and the d(CGCGAATTCGCG)2 duplex. Similar energy calculations have also been performed on complexes with closely related pentamidine analogs, using the complex with the parent drug as the starting point. The resulting structures of the drug-DNA complexes and their energetics have been examined and are compared with the reported DNA binding affinities. These studies provide rationalizations for the differences in binding behavior of pentamidine analogs with differing linker chain lengths and aromatic ring substitutions.