title: Assessment of Atomic Charge Models for Gas-Phase Computations on Polypeptides.
abstract: The concept of the atomic charge is extensively used to model the electrostatic properties of proteins. Atomic charges are not only the basis for the electrostatic energy term in biomolecular force fields but are also derived from quantum mechanical computations on protein fragments to get more insight into their electronic structure. Unfortunately there are many atomic charge schemes which lead to significantly different results, and it is not trivial to determine which scheme is most suitable for biomolecular studies. Therefore, we present an extensive methodological benchmark using a selection of atomic charge schemes [Mulliken, natural, restrained electrostatic potential, Hirshfeld-I, electronegativity equalization method (EEM), and split-charge equilibration (SQE)] applied to two sets of penta-alanine conformers. Our analysis clearly shows that Hirshfeld-I charges offer the best compromise between transferability (robustness with respect to conformational changes) and the ability to reproduce electrostatic properties of the penta-alanine. The benchmark also considers two charge equilibration models (EEM and SQE), which both clearly fail to describe the locally charged moieties in the zwitterionic form of penta-alanine. This issue is analyzed in detail because charge equilibration models are computationally much more attractive than the Hirshfeld-I scheme. Based on the latter analysis, a straightforward extension of the SQE model is proposed, SQE+Q(0), that is suitable to describe biological systems bearing many locally charged functional groups.
authors.affiliation: Center For Molecular Modeling, Ghent University , Technologiepark 903, 9050 Zwijnaarde, Belgium (Member of the QCMM Ghent-Brussels Alliance Group).
authors.forename: Toon
authors.initials: T
authors.lastname: Verstraelen
authors.affiliation: Center For Molecular Modeling, Ghent University , Technologiepark 903, 9050 Zwijnaarde, Belgium (Member of the QCMM Ghent-Brussels Alliance Group).
authors.forename: Ewald
authors.initials: E
authors.lastname: Pauwels
authors.affiliation: Department of General Chemistry (ALGC), Free University of Brussels-VUB , Pleinlaan 2, 1050 Brussels, Belgium (Member of the QCMM Ghent-Brussels Alliance Group).
authors.forename: Frank
authors.initials: F
authors.lastname: De Proft
authors.affiliation: Center For Molecular Modeling, Ghent University , Technologiepark 903, 9050 Zwijnaarde, Belgium (Member of the QCMM Ghent-Brussels Alliance Group).
authors.forename: Veronique
authors.initials: V
authors.lastname: Van Speybroeck
authors.affiliation: Department of General Chemistry (ALGC), Free University of Brussels-VUB , Pleinlaan 2, 1050 Brussels, Belgium (Member of the QCMM Ghent-Brussels Alliance Group).
authors.forename: Paul
authors.initials: P
authors.lastname: Geerlings
authors.affiliation: Center For Molecular Modeling, Ghent University , Technologiepark 903, 9050 Zwijnaarde, Belgium (Member of the QCMM Ghent-Brussels Alliance Group).
authors.forename: Michel
authors.initials: M
authors.lastname: Waroquier