Graphical analysis of pH-dependent properties of proteins predicted using PROPKA

Michal Piotr Rostkowski, Mats Henrik Mikael Olsson, Chresten Rauff Søndergaard, Jan Halborg Jensen

206 Citations (Scopus)

Abstract

Background: Charge states of ionizable residues in proteins determine their pH-dependent properties through their pKavalues. Thus, various theoretical methods to determine ionization constants of residues in biological systems have been developed. One of the more widely used approaches for predicting pKavalues in proteins is the PROPKA program, which provides convenient structural rationalization of the predicted pK avalues without any additional calculations. Results: The PROPKA Graphical User Interface (GUI) is a new tool for studying the pH-dependent properties of proteins such as charge and stabilization energy. It facilitates a quantitative analysis of pKavalues of ionizable residues together with their structural determinants by providing a direct link between the pKadata, predicted by the PROPKA calculations, and the structure via the Visual Molecular Dynamics (VMD) program. The GUI also calculates contributions to the pH-dependent unfolding free energy at a given pH for each ionizable group in the protein. Moreover, the PROPKA-computed pK avalues or energy contributions of the ionizable residues in question can be displayed interactively. The PROPKA GUI can also be used for comparing pH-dependent properties of more than one structure at the same time. Conclusions: The GUI considerably extends the analysis and validation possibilities of the PROPKA approach. The PROPKA GUI can conveniently be used to investigate ionizable groups, and their interactions, of residues with significantly perturbed pKavalues or residues that contribute to the stabilization energy the most. Charge-dependent properties can be studied either for a single protein or simultaneously with other homologous structures, which makes it a helpful tool, for instance, in protein design studies or structure-based function predictions. The GUI is implemented as a Tcl/Tk plug-in for VMD, and can be obtained online at http://propka.ki.ku.dk/∼luca/wiki/ index.php/GUI-Web.

Original languageEnglish
JournalB M C Structural Biology
Volume11
Issue number6
ISSN1472-6807
Publication statusPublished - 2011

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