How accurate can a force field become? A polarizable multipole model combined with fragment-wise quantum-mechanical calculations.
A new method to accurately estimate the interaction energy between a large molecule and a smaller ligand is presented. The method approximates the electrostatic and induction contributions classically by multipole and polarizability expansions, but uses explicit quantum-mechanical fragment calculations for the remaining (nonclassical) contributions, mainly dispersion and exchange repulsion. Thus, it represents a limit of how accurate a force field can ever become for interaction energies if pairwise additivity of the nonclassical term is assumed (e.g., all general-purpose force fields). The accuracy is tested by considering protein-ligand model systems for which the true MP2/6-31G* interaction energies can be computed. The method is shown to be more accurate than related fragmentation approaches. The remaining error (2-5 and approximately10 kJ/mol for neutral and charged ligands, respectively) can be decreased by including the polarizing effect from surrounding fragments in the quantum-mechanical calculations.
Söderhjelm
Pär
P
Department of Theoretical Chemistry, Lund University, Chemical Center, POB 124, SE-22100 Lund, Sweden. par.soderhjelm@teokem.lu.se
Ryde
Ulf
U
D008956:Models, Chemical; D011789:Quantum Theory; D012680:Sensitivity and Specificity; D055672:Static Electricity