The parmbsc0 force field was applied to study in detail the binding of netropsin, at a salt concentration of 0.28 M Na+, to the minor groove of an 8-mer (5'CCAATTGG)(2) DNA duplex forming a netropsin DNA complex which previously has been characterized by X-ray crystallography, albeit with the use of closely related DNA duplexes. The X-ray structure revealed that the terminal guanidinium and amidinium groups of netropsin interact with the extreme ends of the palindromic AATT sequence of the receptor DNA. The parmbsc0 parameters of B-DNA and AMBER v9 parameters of netropsin generated a stable 6 ns molecular dynamics (MD) trajectory for a 1:1 class I binding motif of this complex. Trajectory analysis for the salt and hydration effects on the binding of netropsin to the 8-mer DNA duplex revealed that 18 water molecules and 2 Na+. are displaced from the DNA upon netropsin binding. A hydration density map of the complex parallels the X-ray data showing that two structured water molecules are localized near the netropsin guanidinium and amidinium groups forming H-bond bridges between the receptor and the ligand. (C) 2011 Elsevier B.V. All rights reserved.