Application of New QM/MM Interface to Study of Ru Drugs Interacting with DNA

Zdeněk Futera, Jaroslav V. Burda

New program interface capable to inter-connect standard QM and MM software to perform hybrid QM/MM calculations on molecular systems was implemented. Subtractive QM/MM scheme with link atoms and electronic embedding is used. Several geometry optimization and molecular dynamics algorithms are coded into the interface. Advantage of this system is its flexibility to combine the most suitable programs or methods for description of all parts of computational model.

The QM/MM technique was applied on problem of studying interaction of Ru(II) piano-stool complexes with DNA. The interaction is interesting and important because of significant anti-cancer activity of these complexes caused probably by structural changes of DNA. Interaction with DNA was proven by experimental measurements but the precise reaction mechanism at molecular level is not known. We use DFT(B3LYP) for calculation of properties on Ru(II) complex and nearest nucleic bases (guanines) and Amber FF03 for DNA parametrization.

The reaction energy profile obtained from relaxed and optimized structures will be presented as well as basic properties such as geometry parameters, molecular orbitals or atomic charge analysis. Also size effect of arene ligand will be discussed.