Importance of the Ion-Pair Interactions in the OPEP Coarse-Grained Force Field: Parametrization and Validation

We have derived new effective interactions that improve the description of ion pairs in the Optimized Potential for Efficient protein structure Prediction (OPEP) coarse-grained force field without introducing explicit electrostatic terms. The iterative Boltzmann inversion method was used to extract these potentials from all-atom simulations by targeting the radial distribution function of the distance between the center of mass of the side chains. The new potentials have been tested on several systems that differ in structural properties, thermodynamic stabilities, and number of ion pairs. Our modeling, by refining the packing of the charged amino acids, impacts the stability of secondary structure motifs and the population of intermediate states during temperature folding/unfolding; it also improves the aggregation propensity of peptides. The new version of the OPEP force field has the potentiality to describe more realistically a large spectrum of situations where salt-bridges are key interactions.