Synthetic molecules that target the major groove in a sequence-selective way are a major goal in molecular medicine. Recently a major step has been taken toward achieving this goal: a novel cylinder has been developed that binds strongly into the major groove of DNA. Experimental techniques have provided some information regarding the binding strength and preferred binding sites of the cylinder on DNA. From all the experimental data it is clear that the parent cylinder binds in the major groove and is able to induce dramatic conformational changes in the DNA; these are unprecedented effects with synthetic DNA binders. However, gaining molecular level information in such a macromolecular system is challenging. Molecular dynamics (MD) simulations can provide information at the molecular level that is complementary to experiment and therefore are an ideal way to get a better understanding of this system. In this work we present the results of various MD simulations designed to probe the DNA-cylinder system. We have studied the effect of using CHARMM22 and CHARMM27 as the force-field for the simulations. Results showed that uncomplexed DNA simulated with CHARMM22 was less stable in the B-form than the comparable strand of DNA simulated with CHARMM27. Investigations into the effects of the cylinders charge and shape are also reported. Multi-nanosecond simulations were performed using two related synthetic cylinders, one with two Fe(II) metal centers and the other with two Cu(I) centers, and DNA. Finally the role of DNA within the system was investigated by performing a series of simulations of the cylinders with d(ATATATATATAT)2, d(CGCGCGCGCGCG)2 and d(CGCGCATATACG). Simulations with these DNA strands has only produced one system (CCu2+ with d(ATATATATATAT)) where the cylinder causes a conformational change in the DNA.