Poster Presenter

Semempirical Qm Methods Corrected For Noncovalent Interactions
Jan Rezac, Martin Korth and Pavel Hobza
Czech Republic

The success of the computer-aided drug design depends on reliable scoring - a calculation-based estimate of binding free energy between the drug and its receptor. The key part of this calculation is accurate evaluation of binding energy.

Suitable computational method must be both accurate and efficient. We present a novel approach based on semiempirical quantum mechanical (SE-QM) methods. The advantage of SE-QM over widely used molecular mechanics is better transferability, robustness and the ability to describe the quantum mechanical effects arising from the electronic structure of the molecule. However, SE-QM methods themselves fail to describe accurately noncovalent interactions that play a crucial role in the studied problem. We introduce additional corrections [1,2] covering both of these problematic types of interaction, London dispersion and hydrogen bonds. The corrections are applied to several SE-QM methods, the best results are achieved with the recent PM6 model. Resulting augmented methods (labeled -DH2) reach chemical accuracy (1 kcal/mol) for model molecular complexes, and perform well in application to protein-ligand interactions.

References:

1. Rezac J., Fanfrlik J., Salahub D., Hobza P., J. Chem. Theor. Comput. 5 (7), 1749-1760, 2009

2. Korth M., Ptitonak M., Rezac J., Hobza P., J. Chem. Theor. Comput., in press.