- Protein pKa calculations
In
computational biology , protein pKa calculations are used to estimate the pKa values ofamino acid s as they exist withinprotein s. These calculations complement the pKa values reported for amino acids in their free state, and are used frequently within the fields ofmolecular modeling ,structural bioinformatics , andcomputational biology .Amino acid pKa values
pKa values of amino acid
side chain s play an important role in defining the pH-dependent characteristics of a protein. The pH-dependence of the activity displayed byenzyme s and the pH-dependence ofprotein stability , for example, are properties that are determined by the pKa values of amino acid side chains.The pKa values of an amino acid side chain in solution is typically inferred from the pKa values of model compounds (compounds that are similar to the side chains of amino acids). ("See
Amino acid for the pKa values of all amino acid side chains inferred in such a way.) The table below lists the model pKa values that are normally used in a protein pKa calculation.The effect of the protein environment
When a protein folds, the titratable amino acids in the protein are transferred from a solution-like environment to an environment determined by the 3-dimensional structure of the protein. For example, in an unfolded protein an Aspartic acid typically is in an environment which exposes the titratable side chain to water. When the protein folds the Aspartic acid could find itself buried deep in the protein interior with no exposure to solvent.Furthermore, in the folded protein the Aspartic acid will be closer to other titratable groups in the protein and will also interact with permanent charges (e.g. ions) and dipoles in the protein.All of these effects alter the pKa value of the amino acid side chain, and pKa calculation methods generally calculate the effect of the protein environment on the model pKa value of an amino acid side chain.
Typically the effects of the protein environment on the amino acid pKa value are divided into pH-independent effects and pH-dependent effects. The pH-independent effects (desolvation, interactions with permanent charges and dipoles) are added to the model pKa value to give the intrinsic pKa value. The pH-dependent effects cannot be added in the same straight-forward way and have to be accounted for using Boltzmann summation, Tanford-Roxby iterations or other methods.
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