The hydration of serine: multipole moments versus point charges

Abstract

Next-generation force fields must incorporate improved electrostatic potentials in order to increase the reliability of their predictions. A crucial decision toward this goal is to abandon point charges in favour of multipole moments centered on nuclear sites. Here we compare the geometries generated by quantum topological multipole moments with those generated by four popular point charge models (TAFF, OPLS-AA, MMFF94x and PFROSST) for a hydrated serine. A main feature of this study is the dual comparison made, both at static level (geometry optimisation via energy minimisation) and at dynamic level (via molecular dynamics and radial/spatial distribution function analysis). At static level, multipolar electrostatics best reproduces the ab initio reference geometry. At dynamic level, multipolar electrostatics produces more structure than point charge electrostatics does, over the whole range. From our previous work on liquid water [Int. J. Quantum. Chem., 2004, 99, 685], where agreement with experiment only occurs when using multipole moments, we deduce that our predictions for hydrated serine will also be closer to experiment when using multipolar electrostatics. The spatial distribution function shows that only multipolar electrostatics shows pronounced structure at long range. Even at short range there are many regions where waters appear in the system governed by multipolar electrostatics but not in that governed by point charges.