NEEMP: software for validation, accurate calculation and fast parameterization of EEM charges.
BACKGROUND
The concept of partial atomic charges was first applied in physical and organic chemistry and was later also adopted in computational chemistry, bioinformatics and chemoinformatics. The electronegativity equalization method (EEM) is the most frequently used approach for calculating partial atomic charges. EEM is fast and its accuracy is comparable to the quantum mechanical charge calculation method for which it was parameterized. Several EEM parameter sets for various types of molecules and QM charge calculation approaches have been published and new ones are still needed and produced. Methodologies for EEM parameterization have been described in a few articles, but a software tool for EEM parameterization and EEM parameter sets validation has not been available until now.


RESULTS
We provide the software tool NEEMP (http://ncbr.muni.cz/NEEMP), which offers three main functionalities: EEM parameterization [via linear regression (LR) and differential evolution with local minimization (DE-MIN)]; EEM parameter set validation (i.e., validation of coverage and quality) and EEM charge calculation. NEEMP functionality is shown using a parameterization and a validation case study. The parameterization case study demonstrated that LR is an appropriate approach for smaller and homogeneous datasets and DE-MIN is a suitable solution for larger and heterogeneous datasets. The validation case study showed that EEM parameter set coverage and quality can still be problematic. Therefore, it makes sense to verify the coverage and quality of EEM parameter sets before their use, and NEEMP is an appropriate tool for such verification. Moreover, it seems from both case studies that new EEM parameterizations need to be performed and new EEM parameter sets obtained with high quality and coverage for key structural databases.


CONCLUSIONS
We provide the software tool NEEMP, which is to the best of our knowledge the only available software package that enables EEM parameterization and EEM parameter set validation. Additionally, its DE-MIN parameterization method is an innovative approach, developed by ourselves and first published in this work. In addition, we also prepared four high-quality EEM parameter sets tailored to ligand molecules.Graphical abstract.
CEITEC - Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic ; National Centre for Biomolecular Research, Faculty of Science, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic ; Faculty of Informatics, Masaryk University Brno, Botanická 68a, 602 00 Brno, Czech Republic.
Tomáš
T
Raček
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.
Jana
J
Pazúriková
CEITEC - Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic ; National Centre for Biomolecular Research, Faculty of Science, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
Radka
R
Svobodová Vařeková
CEITEC - Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic ; National Centre for Biomolecular Research, Faculty of Science, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
Stanislav
S
Geidl
CEITEC - Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic ; Institute of Computer Science, Masaryk University Brno, Botanická 68a, 602 00 Brno, Czech Republic.
Aleš
A
Křenek
CEITEC - Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
Francesco Luca
FL
Falginella
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.
Vladimír
V
Horský
CEITEC - Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
Václav
V
Hejret
CEITEC - Central European Institute of Technology, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic ; National Centre for Biomolecular Research, Faculty of Science, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
Jaroslav
J
Koča
EEM; EEM parameterization; Electronegativity equalization method; Partial atomic charges; wwPDB CCD database