title: 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].
authors.affiliation: Laboratoire de Physico-Chimie Informatique, Unité de Chimie Physique Théorique et Structurale, University of Namur (FUNDP), Rue de Bruxelles 61, 5000 Namur, Belgium. laurence.leherte@fundp.ac.be
authors.forename: Laurence
authors.initials: L
authors.lastname: Leherte
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Vercauteren
mesh_terms: D000465:Algorithms; D000596:Amino Acids / Q000737:chemistry*; D003198:Computer Simulation; D008958:Models, Molecular; D008968:Molecular Conformation; D010455:Peptides / Q000737:chemistry*; D015221:Potassium Channels / Q000737:chemistry*; D011506:Proteins / Q000737:chemistry*; D012996:Solutions / Q000737:chemistry; D055672:Static Electricity; D013499:Surface Properties; D013816:Thermodynamics; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D010455:Peptides; D015221:Potassium Channels; D011506:Proteins; D012996:Solutions; D016159:Tumor Suppressor Protein p53