Poster Presentation 2014 International Biophysics Congress

Accurate charges for docking of metalloproteins (#555)

Ki Chul Park 1 , Art Cho
  1. korea university, Sejong City, South Korea
Modeling of binding between metalloproteins and small molecules is generally regarded as a difficult problem. In particular, most of the current docking programs are ineffective in finding the correct binding poses when metalloproteins are involved. It was found in our previous research that the difficulty stems from inadequate partial charges used for docking with force field based energy scoring. We had devised a method in which partial charges on metal ions along with surrounding protein atoms are rescaled after QM/MM energy calculations before docking with the new charges. The method proved to be quite successful in describing correct binding modes of ligands in binding sites with metal atoms but rather cumbersome to perform and costly to be practical. In an attempt to conceive a docking protocol that retains the same spirit as our previous method and yet can be practical, we tested a few different implementations of combining QM/MM calculations with force field docking. The results show that a proper pre-docking charge rescaling through QM/MM calculations combined with QM/MM docking with minimum QM region can yield compatible accuracies as our previous method.