Charge density distributions derived from smoothed electrostatic potential functions: design of protein reduced point charge models

Abstract

To generate reduced point charge models of proteins, we developed an original approach to hierarchically locate extrema in charge density distribution functions built from the Poisson equation applied to smoothed molecular electrostatic potential (MEP) functions. A charge fitting program was used to assign charge values to the so-obtained reduced representations. In continuation to a previous work, the Amber99 force field was selected. To easily generate reduced point charge models for protein structures, a library of amino acid templates was designed. Applications to four small peptides, a set of 53 protein structures, and four KcsA ion channel models, are presented. Electrostatic potential and solvation free energy values generated by the reduced models are compared with the corresponding values obtained using the original set of atomic charges. Results are in closer agreement with the original all-atom electrostatic properties than those obtained with a previous reduced model that was directly built from the smoothed MEP functions [Leherte and Vercauteren in J Chem Theory Comput 5:3279-3298, 2009].

Unveiling GruPol: Predicting Electric and Electrostatic Properties of Macromolecules via the Building Block Approach

“…The estimation of electrostatic potential (ESP) in large molecules is commonly performed using charge distribution methods . Nevertheless, that is not the only possible route.…”

“…The estimation of electrostatic potential (ESP) in large molecules is commonly performed using charge distribution methods. 39 Nevertheless, that is not the only possible route. Our recent studies 12 have shown that for small peptides, instead of atomic charges, one can use atomic dipole moments and anyway accurately reproduce the ESP calculated through quantum methods, particularly in regions close to the limits of the van der Waals radii.…”

Reduced point charge models of proteins: assessment based on molecular dynamics simulations

“…This implies that if one studies, for instance, rigid systems by freezing dihedrals, the RPCMs should be well suited for electrostatic calculations, as already shown in our work about potassium ion channels. [18,49] Coulomb shortrange (Cb_SR) regression data behave a lot better, with R and S close to 1. One even notices that while the intramolecular protein-protein Cb_SR ( p-p) slope is almost always , 1, the intermolecular protein -nonprotein Cb_SR ( p-np) slope can be .…”