S3: Protein-ligand interaction

Higher order electrostatics for protein-ligand interaction
Stan Wlodek, Senior Scientist, OpenEye Scientific Software

Stan Wlodek, Senior Scientist


OpenEye Scientific Software


Stan Wlodek and Laszlo Fusti-Molnar


A method for obtaining electrostatic multipoles for protein-ligand systems is proposed. Atomic multipoles (up to octupoles) are calculated with GAMESS using the Distributed Multipole Analysis (DMA) method. The multipoles are subsequently used for the Coulomb term in our new intermolecular force field (IEFF).

IEFF is used for the estimation of protein-ligand interaction energies and ligand poses. The protein is fragmented into either capped mono-residue or tripeptides. Using 12-20 residues model systems, we compare both mono-residue/tripeptide approximations to the entire protein calculation.

We show that the tripeptide approximation for calculating atomic multipoles is significantly more reliable for the estimation of protein-ligand interaction energy, while the differences between mono-residue/tripeptide are smaller for pose predictions.

The usage of the proposed potential is illustrated for both hydrophobic and water mediated binding.