Use of the parmbsc0 force field and trajectory analysis to study the binding of netropsin to the DNA fragment (5′CCAATTGG)2 in the presence of excess NaCl salt in aqueous solution

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.