A many-body model to study protein. Incidence of cooperative effects on the interactions of the calmodulin protein with four Ca dications and with a target enzyme peptide.

Great efforts were devoted in the past years in developing empirical force fields to investigate proteinic systems (such as CHARMM and AMBER), all based on two-body interatomic potentials. However, because of the great incidence of cooperative effects on two fundamental microscopic interactions (i.e. hydrogen bonding and polarization phenomena), such potentials are expected to not be enough accurate to describe, in particular, proteinic systems interacting with mono-atomic ions. We have developped a new class of force-field (called TCPEp) where two specific many-body interatomic potentials are introduced to model both hydrogen bonding and polarization effects. This new force-field has been applied to investigate the origin of the interactions among the calmodulin protein, four Ca2+ dications and a calmodulin target enzyme peptide. The possible improvements arising from using a many-body potential to describe biological macromolecules will be discussed, in particular, by comparing the TCPEp results regarding the above calmodulin system to those obtained with the classical two-body CHARMM potential.