title: High-quality and universal empirical atomic charges for chemoinformatics applications.
abstract: BACKGROUND
  Partial atomic charges describe the distribution of electron density in a molecule and therefore provide clues to the chemical behaviour of molecules. Recently, these charges have become popular in chemoinformatics, as they are informative descriptors that can be utilised in pharmacophore design, virtual screening, similarity searches etc. Especially conformationally-dependent charges perform very successfully. In particular, their fast and accurate calculation via the Electronegativity Equalization Method (EEM) seems very promising for chemoinformatics applications. Unfortunately, published EEM parameter sets include only parameters for basic atom types and they often miss parameters for halogens, phosphorus, sulphur, triple bonded carbon etc. Therefore their applicability for drug-like molecules is limited.
  
  
  RESULTS
  We have prepared six EEM parameter sets which enable the user to calculate EEM charges in a quality comparable to quantum mechanics (QM) charges based on the most common charge calculation schemes (i.e., MPA, NPA and AIM) and a robust QM approach (HF/6-311G, B3LYP/6-311G). The calculated EEM parameters exhibited very good quality on a training set ([Formula: see text]) and also on a test set ([Formula: see text]). They are applicable for at least 95 % of molecules in key drug databases (DrugBank, ChEMBL, Pubchem and ZINC) compared to less than 60 % of the molecules from these databases for which currently used EEM parameters are applicable.
  
  
  CONCLUSIONS
  We developed EEM parameters enabling the fast calculation of high-quality partial atomic charges for almost all drug-like molecules. In parallel, we provide a software solution for their easy computation (http://ncbr.muni.cz/eem_parameters). It enables the direct application of EEM in chemoinformatics.
authors.affiliation: National Centre for Biomolecular Research, Faculty of Science and CEITEC, Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
authors.forename: Stanislav
authors.initials: S
authors.lastname: Geidl
authors.affiliation: National Centre for Biomolecular Research, Faculty of Science and CEITEC, Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Bouchal
authors.affiliation: National Centre for Biomolecular Research, Faculty of Science and CEITEC, Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic ; Faculty of Informatics, Masaryk University Brno, Botanická 68a, 602 00 Brno, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Raček
authors.affiliation: National Centre for Biomolecular Research, Faculty of Science and CEITEC, Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
authors.forename: Radka
authors.initials: R
authors.lastname: Svobodová Vařeková
authors.affiliation: National Centre for Biomolecular Research, Faculty of Science and CEITEC, Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
authors.forename: Václav
authors.initials: V
authors.lastname: Hejret
authors.affiliation: Institute of Computer Science, Masaryk University Brno, Botanická 68a, 602 00 Brno, Czech Republic.
authors.forename: Aleš
authors.initials: A
authors.lastname: Křenek
authors.affiliation: Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, 9500 Gilman Drive, San Diego, MC 0657 USA.
authors.forename: Ruben
authors.initials: R
authors.lastname: Abagyan
authors.affiliation: National Centre for Biomolecular Research, Faculty of Science and CEITEC, Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Koča
keywords: Drug-like molecules; EEM; Electronegativity Equalization Method; Partial atomic charges; QM; Quantum mechanics