Application of semiempirical quantum chemical methods as a scoring function in docking

A crucial point in docking simulations is the scoring function used for estimation of the target-ligand interaction energy. The usual practice is to employ fast but simplified empirical scoring functions. Rigorous quantum chemical methods are too slow to screen virtual combinatorial libraries consisting of thousands of molecules, but they can be used in the final step of the simulations for assessing the results obtained. At this stage quantum chemical calculations can be performed only for the 10-100 top binders predicted by simplified scoring functions, and only using linear-scaling semiempirical quantum chemical methods such as MOZYME. The possibilities and potentialities of the quantum chemical methods for estimation of the binding affinities in docking simulations are a largely unexplored area, so the main goal of this study is a detailed evaluation of the potential and limitations of the MOZYME methodology for estimation of the target-ligand binding energies and its comparison with available experimental data.