Simulation of <i>Eco</i>RI Dodecamer Netropsin Complex Confirms Class I Complexation Mode

Abstract

The knowledge of the exact positions of ligands complexed to DNA is essential for systematic modeling of new antitumor drugs controlling transcription. In the case of the EcoRI dodecamer netropsin complex (= Nt/(CGCGAATTCGCG)2 complex), experimental techniques yield contradicting results about the drug position. Hence, we have investigated the Nt/(CGCGAATTCGCG)2 complex by a 5 ns molecular dynamics simulation to shed light onto the binding mode. Analysis of the simulation confirms in agreement with NMR data and X-ray results that the Nt/(CGCGAATTCGCG)2 complex exists as a class I complex, although the simulation was started from class II conformation suggested by alternative X-ray investigations. Additionally, the simulation revealed stable conformations of the complexed netropsin molecule, providing new contact information that may be important for the design of new potential ligands.