PKA17—A Coarse-Grain Grid-Based Methodology and Web-Based Software for Predicting Protein pK a Shifts

We have developed and tested PKA17, a coarse-grain grid-based model for predicting protein pK _a shifts. Our pK _a predictor is currently deployed via a website interface. We have carried out parameter fitting using 442 Asp, Glu, His, Lys, and Arg residues for which experimental results are available in the literature. PROPKA software has been used for benchmarking. The average unsigned error and root-mean-square deviation (RMSD) have been found to be 0.628 and 0.831 pH units, respectively, for PKA17. The corresponding results with PROPKA are 0.761 and 1.063 units. We have assessed the robustness of the developed PKA17 methodology with a number of tests and have also explored the possibility of using a combination of PROPKA and PKA17 calculations in order to improve the accuracy of predicted pK _a values for protein residues. We have also once again confirmed that protein acidity constants are influenced almost entirely by residues in the immediate spatial proximity of the ionizable amino acids. The resulting PKA17 software has been deployed online with a web-based interface at http://users.wpi.edu/~jpcvitkovic/pka_calc.html . © 2019 Wiley Periodicals, Inc.