Maceuticals. JC, CP, and IM are personnel of Bayer HealthCare Pharmaceuticals. CP owns stock in Bayer AG. CK is definitely an employee of Bayer Pharma AG. MJS has received consultancy costs and analysis help from Bayer HealthCare Pharmaceuticals and Eisai; consultancy fees/honorarium and research assistance from AstraZeneca and GenzymeSanofi; consultancy charges from Exelixis; and consultancy fees/honorarium from Sobi.Author Manuscript Author Manuscript Author Manuscript Author Manuscript
SvobodovVaekovet al. Journal of Cheminformatics 2013, five:18 a r a http://www.jcheminf.com/content/5/RESEARCH ARTICLEOpen AccessPredicting pKa values from EEM atomic chargesRadka SvobodovVaekov1 , Stanislav Geidl1 , CrinaMaria Ionescu1 , Ondej Skehota1 , a r a r r c Toms Bouchal1 , David Sehnal1 , Ruben Abagyan2 and Jaroslav Ko a1 aAbstract The acid dissociation continual pKa is usually a crucial molecular house, and there’s a sturdy interest in the improvement of trusted and quickly strategies for pKa prediction. We’ve evaluated the pKa prediction capabilities of QSPR models primarily based on empirical atomic charges calculated by the Electronegativity Equalization Technique (EEM). Specifically, we collected 18 EEM parameter sets made for eight different quantum mechanical (QM) charge calculation schemes. Afterwards, we prepared a education set of 74 substituted phenols. In addition, for each and every molecule we generated its dissociated type by removing the phenolic hydrogen. For all the molecules in the instruction set, we then calculated EEM charges employing the 18 parameter sets, as well as the QM charges making use of the eight above pointed out charge calculation schemes.1031967-52-8 Order For each and every sort of QM and EEM charges, we developed one QSPR model employing charges from the nondissociated molecules (three descriptor QSPR models), and one particular QSPR model primarily based on charges from both dissociated and nondissociated molecules (QSPR models with five descriptors).Formula of (S)-2-Amino-2,4-dimethylpentan-1-ol Afterwards, we calculated the high quality criteria and evaluated all the QSPR models obtained.PMID:24120168 We located that QSPR models employing the EEM charges proved as a superb method for the prediction of pKa (63 of those models had R2 0.9, whilst the best had R2 = 0.924). As expected, QM QSPR models supplied extra accurate pKa predictions than the EEM QSPR models but the differences weren’t substantial. In addition, a massive advantage from the EEM QSPR models is the fact that their descriptors (i.e., EEM atomic charges) may be calculated markedly faster than the QM charge descriptors. Moreover, we located that the EEM QSPR models are certainly not so strongly influenced by the selection of the charge calculation approach as the QM QSPR models. The robustness in the EEM QSPR models was subsequently confirmed by crossvalidation. The applicability of EEM QSPR models for other chemical classes was illustrated by a case study focused on carboxylic acids. In summary, EEM QSPR models constitute a rapidly and precise pKa prediction approach which can be applied in virtual screening.Key phrases: Dissociation continual, Quantitative structureproperty connection, QSPR, Partial atomic charges, Electronegativity equalization process, EEM, Quantum mechanics, QMBackgroundThe acid dissociation continual pKa is an essential molecular home, and its values are of interest in pharmaceutical, chemical, biological and environmental research. The pKa values have identified application in quite a few regions, including the evaluation and optimization of candidate drug molecules [13], ADME profiling [4,5], pharmacokinetics [6], understanding of proteinligand in.
