Knowledge of the possible ionization states of a pharmaceutical substance, embodied in the pKa values (logarithm of the acid dissociation constant), is vital for understanding many properties essential to drug development. We compare nine commercially available or free programs for predicting ionization constants. Eight of these programs are based on empirical methods: ACD/pKa DB 12.0, ADME Boxes 4.9, ADMET Predictor 3.0, Epik 1.6, Marvin 5.1.4, Pallas pKalc Net 2.0, Pipeline Pilot 5.0, and SPARC 4.2; one program is based on a quantum chemical method: Jaguar 7.5. We compared their performances by applying them to 197 pharmaceutical substances with 261 carefully determined and highly reliable experimental pKa values from a literature source. The programs ADME Boxes 4.9, ACD/pKa DB 12.0, and SPARC 4.2 ranked as the top three with mean absolute deviations of 0.389, 0.478, and 0.651 and r2 values of 0.944, 0.908, and 0.894, respectively. ACD/pKa DB 12.0 predicted all sites, whereas ADME Boxes 4.9 and SPARC 4.2 failed to predict 5 and 18 sites, respectively. The performance of the quantum chemical-based program Jaguar 7.5 was not as expected, with a mean absolute deviation of 1.283 and an r2 value of 0.579, indicating the potential for further development of this type of approach to pKa prediction.
Visit publication
Comparison of Nine Programs Predicting pKa Values of Pharmaceutical Substances
Posted by
Chenzong Liao
on 12 09 2011
Related content
03 10 2022
< 1 minute
Calculate on the cloud
In order to increase the flexibility, access and integrability, Calculators and Predictors have...
12 05 2022
< 1 minute
Coupling stabilizers open KV1-type potassium channels
ABSTRACT: The opening and closing of voltage-gated ion channels are regulated by voltage sensors...
13 11 2021
< 1 minute
Cheminfo Stories 2021 Virtual UGM | Boost analytical experiments with phys-chem properties
TRY CHEMICALIZE Log in for videos & slides
13 11 2021
< 1 minute
Cheminfo Stories 2021 Virtual UGM | Enhancing Sibylla’s innovative drug discovery platform with ChemAxon
Sibylla's innovative pharmacological platform is aimed at discovering new drugs for untreatable...