Determination of protein coarse-grain charges from smoothed molecular electrostatic potentials

The design of protein coarse-grain (CG) models and their corresponding interaction potentials is currently an active field of research, especially for solving protein folding or docking problems, … Among the essential parameters involved by CG potentials, electrostatics interactions are of crucial importance since they govern local and global properties such as their stability, their flexibility, …

Following our development of an original approach to decompose hierarchically a protein structure into fragments from its electron density (ED) distribution [1,2], we propose to apply our method to molecular electrostatic potential functions (MEP), calculated from point charges as implemented in well-known force fields. To follow the pattern of local maxima (and minima) in an ED or a MEP distribution, as a function of the degree of smoothing, we adopted the following strategy. First, each atom of a molecule is considered as a starting point (a peak, or a pit for negative charges in a MEP analysis). As the smoothing degree increases, each point moves along a path to reach a location where the ED or MEP gradient value vanishes. Convergences of trajectories lead to a reduction of the number of points.

Practically, to determine the protein backbone representations, we analyze CG models obtained for a strand of polyglycine. The influence of the different amino acid side chains is then studied for different rotamers by substituting the central glycine residue. A fitting algorithm is used to assign charges to the obtained local maxima/minima.

[1] L. Leherte, Acta Crystallogr. D 60 (2004) 1254
[2] L. Leherte, B. Guillot, D. Vercauteren, V. Pichon-Pesme, Ch. Jelsch, A. Lagoutte, Cl. Lecomte, in “Quantum Theory of Atoms in Molecules - From Solid State to DNA and Drug Design”, Eds C. F. Matta, R. J. Boyd, Wiley-VCH (Weinheim), (2006)