Journal of Computer-Aided Molecular Design

, Volume 25, Issue 10, pp 913–930 | Cite as

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

  • Laurence Leherte
  • Daniel P. Vercauteren


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].


Molecular electrostatic potential Charge density Smoothing Point charge model Coarse grain Protein 



Amino acid


Assisted model building and energy refinement


Adaptive Poisson-Boltzmann Solver


Charge density


Coarse grain(ed)


Center of mass


Desoxyribonucleic acid


Empirical conformational energy program for peptides


Electron density


Force field


Genetic algorithm




Monte Carlo


Molecular dynamics


Molecular mechanics


Molecular electrostatic potential




Protein data bank


Root mean square deviation


Simulated annealing


Structural library of intrinsic residue propensities


Simple molecular mechanics for proteins





The authors thank the referees for very useful comments. They also acknowledge Profs. E. Clementi and M. Sansom for very fruitful discussions, as well as Prof. N. Baker for APBS assistance. The ‘‘Fonds National de la Recherche Scientifique’’ (FNRS-FRFC), the ‘‘Loterie Nationale’’ (convention no. 2.4578.02), and the ‘‘Facultés Universitaires Notre-Dame de la Paix’’ (FUNDP), are gratefully acknowledged for the use of the Interuniversity Scientific Computing Facility (ISCF) Center.

Supplementary material

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© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  1. 1.Laboratoire de Physico-Chimie Informatique, Unité de Chimie Physique Théorique et StructuraleUniversity of Namur (FUNDP)NamurBelgium

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