For docking calculations at different values of pH, I am working with flavonoids and would like to know about any software/server that can prepare ligands depending on the pH. Up to now I read about Maestro (Schrodinger) but it is too expensive for us. I wonder if you could suggest other alternatives.
This is a challenging problem and there are many programs that do this.
One review was published a few years ago: "Comparison of Nine Programs Predicting pKa Values of Pharmaceutical Substances", J. Chem. Inf. Model., 2009, 49 (12), pp 2801–2812
Knowledge of the possible ionization states of a pharmaceutical substance, embodied in the pKa values [...] is vital [...] We compare nine commercially available or free programs for predicting ionization constants. [...] 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 $r^2$ 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.
Surprisingly, the quantum program did poorly.
There's even a full book on the subject: Computational Approaches for the Prediction of pKa Values by George Shields and Paul Seybold. It covers both quantum and QSAR approaches.
Some of the best seem to be:
- ADMET Predictor
- Propka Also available as open source code: https://github.com/jensengroup/propka-3.1
- Marvin / ChemAxon
But there are dozens out there. I'd check the review articles and try a few.
For this, you can try to use the LigpKa database server.
you can use also H++ server just go to this link; http://biophysics.cs.vt.edu/