Calibrating nucleic acids torsional energetics in force-field: Insights from model compounds

The development of force fields that accurately describe both the structure and the dynamics of nucleic acids in condensed phase is an ongoing effort. The development of the latest versions of the CHARMM and AMBER nucleic acids relied on ab initio as well as on experimental target data for the parametrization. Here we compare the two latest versions of the AMBER and CHARMM force field, in their ability to reproduce the ab initio torsional energy surfaces for selected nucleic acid dihedral angles. A series of model compounds is instrumental in this analysis. This illustrates how dissecting the energetics of the force-field with model compounds allows to uncover deficiencies in the force-field, which may or may not be apparent in the simulated properties of the full nucleic acids. The positions of minima, the relative energies and barrier heights are discussed. This type of analysis is proposed as one useful diagnostic criterion, in combination with others, to assess how well balanced are the various contributions to the energetics of a nucleic acid force field. © 2001 Elsevier Science B.V.