Simulation of EcoRI dodecamer netropsin complex confirms class I complexation mode

The knowledge of the exact positions of ligands complexed to DNA is essenti al for systematic modeling of new antitumor drugs controlling transcription . In the case of the EcoRI dodecamer netropsin complex (= Nt/(CGCGAATTCCrCC r)(2) complex), experimental techniques yield contradicting results about t he drug position. Hence, we have investigated the Nt/(CGCGAATTCGCG)(2) comp lex 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/(CCCGAATTCGCG)(2) complex exists as a class I compl ex, although the simulation was started from class II conformation suggeste d by alternative X-ray investigations. Additionally, the simulation reveale d stable conformations of the complexed netropsin molecule, providing new c ontact information that may be important for the design of new potential li gands.