Informace o publikaci

High-quality and universal empirical atomic charges for chemoinformatics applications

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GEIDL Stanislav BOUCHAL Tomáš RAČEK Tomáš SVOBODOVÁ VAŘEKOVÁ Radka HEJRET Václav KŘENEK Aleš ABAGYAN Ruben KOČA Jaroslav

Rok publikování 2015
Druh Článek v odborném periodiku
Časopis / Zdroj Journal of Cheminformatics
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www http://jcheminf.springeropen.com/articles/10.1186/s13321-015-0107-1
Doi http://dx.doi.org/10.1186/s13321-015-0107-1
Obor Biochemie
Klíčová slova Partial atomic charges; Electronegativity Equalization Method; EEM; Quantum mechanics; QM; Drug-like molecules
Popis 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 (R2 > 0.9) and also on a test set (R2 > 0.93). 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. It enables the direct application of EEM in chemoinformatics.
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