The structure, stability, solubility as well as protein folding and function are closely related to their acidity constants (pKa) . Thus fast and accurate pKa predicting computational methods are needed in the protein research and we have previously demonstrated that our novel Fuzzy-Border Continuum solvent model performs well in such calculations. Here, Polarizable Simulations Second-Order Interaction Model (POSSIM) force field was employed along with Fuzzy-Border Continuum solvent model to determine the pKa shifts for carboxylic residues (Asp7, Glu10, Glu19, Asp27 and Glu43) using propanoic acid and butanoic acid as the reference systems of aspartic and glutamic acid respectively. Further the relative pKa values of the basic residues of protein (Lys13, Lys29, Lys34, His52 and Lys55) were determined using n-pentylamine and 4-ethylimidazole as reference systems for lysine and histidine residues respectively. The hydration parameters of the small molecules were first fitted to their solvation energy with overall average error of 0.140kcal/mol at 298.15K. These parameters were used to reproduce the pKa of the reference systems.  The same parameters were employed to calculate the pKa of the individual carboxylic and basic residues of the protein.  The overall average unsigned error in the pKa values of the acid residues is 0.45pH units compared to 0.58pH units for polarizable force field (PFF) and Poisson Boltzmann formalism (PBF) continuum solvation model. The basic pKa calculated using POSSIM/FB was in close agreement to PFF/PBF (with advanced non polar solvation term) with average error of 0.77 and 0.72pH units respectively. These results are produced without any parameterization of the hydration parameters to the pKa value. This shows the good transferability of the fuzzy-border parameters for POSSIM force field and the importance of our explicit electrostatic polarization treatment of the solute molecules in calculating pKa of the protein residues.

Computing acidity constants for turkey ovomucoid third domain protein using POSSIM (polarizable simulations second-order interaction model) force field and Fuzzy-Border (FB) continuum solvation model

248th National Meeting (2014)

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