pK a Calculations in Membrane Proteins from Molecular Dynamics Simulations.

The conformational changes of membrane proteins are crucial to their function and usually lead to fluctuations in the electrostatic environment of the protein surface. A very effective way to quantify these changes is by calculating the pK a values of the protein's titratable residues, which can be regarded as electrostatic probes. To achieve this, we need to take advantage of the fast and reliable pK a calculators developed for globular proteins and adapt them to include the explicit effects of membranes. Here, we provide a detailed linear response approximation protocol that uses our own software (PypKa) to calculate reliable pK a values from short MD simulations of membrane proteins.