A set of empirical rules relating the protein structure to the pK values of ionizable residues have been developed by Li, Robertson, and Jensen. These rules form the basis for the [https://biolib.com/bio-utils/propka/ web-accessible] program called PROPKA for rapid predictions of pK values. A recent empirical pK prediction program was released by Tan KP et.al. with the online server [http://mspc.bii.a-star.edu.sg/tankp/ DEPTH web server].