#Calculate pi of amino acid with r group full#
#Calculate pi of amino acid with r group software#
#Calculate pi of amino acid with r group free#

#Calculate pi of amino acid with r group full#

Molecular dynamics methods of calculating p K a values make it possible to include full flexibility of the titrated molecule. A recent empirical p K a prediction program was released by Tan KP et.al. These rules form the basis for the web-accessible program called PROPKA for rapid predictions of p K a values. Empirical methods Ī set of empirical rules relating the protein structure to the p K a values of ionizable residues have been developed by Li, Robertson, and Jensen. To perform such a calculation, one needs theoretical methods that can calculate the effect of the protein interior on a p K a value, and knowledge of the pKa values of amino acid side chains in their fully solvated states. The H++ web server, the pKD webserver, MCCE2, Karlsberg+, PETIT and GMCT use the FDPB method to compute p K a values of amino acid side chains.įDPB-based methods calculate the change in the p K a value of an amino acid side chain when that side chain is moved from a hypothetical fully solvated state to its position in the protein. The PBE is a modification of Poisson's equation that incorporates a description of the effect of solvent ions on the electrostatic field around a molecule. Some methods are based on solutions to the Poisson–Boltzmann equation (PBE), often referred to as FDPB-based methods ( FDPB stands for ' finite difference Poisson–Boltzmann').

#Calculate pi of amino acid with r group software#

Several software packages and webserver are available for the calculation of protein p K a values. One group is displaying a back-titration event (blue group). The image on the right shows a theoretical system consisting of three acidic residues. The interplay of the intrinsic p K a values of a system with the electrostatic interaction energies between titratable groups can produce quite spectacular effects such as non-Henderson–Hasselbalch titration curves and even back-titration effects. The pH-dependent effects cannot be added in the same straightforward way and have to be accounted for using Boltzmann summation, Tanford–Roxby iterations or other methods. The pH-independent effects (desolvation, interactions with permanent charges and dipoles) are added to the model p K a value to give the intrinsic p K a value. Typically, the effects of the protein environment on the amino acid p K a value are divided into pH-independent effects and pH-dependent effects. All of these effects alter the p K a value of the amino acid side chain, and p K a calculation methods generally calculate the effect of the protein environment on the model p K a value of an amino acid side chain. When the protein folds, the aspartic acid could find itself buried deep in the protein interior with no exposure to solvent.įurthermore, 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. For example, in an unfolded protein, an aspartic acid typically is in an environment which exposes the titratable side chain to water. 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. The black curve shows a back-titration event The effect of the protein environment Ĭoupled system consisting of three acids.

The table below lists the model p K a values that are often used in a protein p K a calculation, and contains a third column based on protein studies. There are also numerous experimental studies that have yielded such values, for example by use of NMR spectroscopy. See Amino acid for the p K a values of all amino acid side chains inferred in such a way.

The p K a values of an amino acid side chain in solution is typically inferred from the p K a values of model compounds (compounds that are similar to the side chains of amino acids). The pH-dependence of the activity displayed by enzymes and the pH-dependence of protein stability, for example, are properties that are determined by the p K a values of amino acid side chains. P K a values of amino acid side chains play an important role in defining the pH-dependent characteristics of a protein.

#Calculate pi of amino acid with r group free#

These calculations complement the p K a values reported for amino acids in their free state, and are used frequently within the fields of molecular modeling, structural bioinformatics, and computational biology. In computational biology, protein p K a calculations are used to estimate the p K a values of amino acids as they exist within proteins.