More examples of the usage of PIPSA 2.0
(Protein Interaction Property Similarity Analysis)

WW Domains

Plastocyanin mutants analysis

Schleinkofer K. , Wiedemann U. , Otte l., Wang T., Krause G., Oschkinat H. and Wade R.C.
Comparative Structural and Energetic Analysis of WW Domain/Peptide Interactions.
J. Mol. Biol. 2004, 344, 865-881.

WW domains are small globular protein interaction modules found in a wide spectrum of proteins. They recognize their target proteins by binding specifically to short linear peptide motifs that are often proline-rich. To understand the determinants of the ligand binding propensities of WW domains, 42 WW domains were analyzed to derive quantitative structure-activity relationships .
From a protein interaction property similarity analysis (PIPSA) of the WW domain structures, a structure-based classification of WW domains is proposed  that expands the existent sequence-based classification scheme.

Representatives of the different classes of WW domains have markedly different electrostatic potentials:
The electrostatic potential is an additional distinguishing feature of WW domains not captured by sequence analysis.  It is conserved among those WW domains interacting with peptides containing charged residues. Consistent with the opposite charge of the specificity determining residue within the ligand (arginine and phospho-serine/phospho-threonine respectively), the Ra- and Rb-group members show a conserved negative potential whereas the poS/poT-group members show a conserved positive potential. On the other hand, the hydrophobic potential is equally important for ligand binding for all WW domains and thus cannot be used as a distinguishing feature.
The results of application of pipsa analysis to the models of WW domains can be found here  (151 MB) .

Plastocyanin mutants analysis

De Rienzo, F., Gabdoulline,R.R., Menziani,M.C., De Benedetti, P.G. and Wade,R.C.
Electrostatic Analysis and Brownian Dynamics Simulation of the Association of Plastocyanin and Cytochrome F
Biophys. J. (2001) 81, 3090-3104.

The oxidation of cytochrome f by the soluble cupredoxin plastocyanin is a central reaction in the photosynthetic electron transfer chain of all oxygenic organisms. Here, two different computational approaches are used to gain new insights into the role of molecular recognition and protein-protein association processes in this redox reaction.
A comparative analysis of the computed molecular electrostatic potentials of seven single and multiple point mutants of spinach plastocyanin (D42N, E43K, E43N, E43Q/D44N, E59K/E60Q, E59K/E60Q/E43N, Q88E) and the wt protein was carried out. The experimentally determined relative rates (k2) for the set of plastocyanin mutants are found to correlate well (r2   0.90   0.97) with the computed measure of the similarity of the plastocyanin electrostatic potentials:

This approach allows to relate similarity indices to observable association rates.  Application of PIPSA to derive this correlation can be downloaded here  (10 MB) .

Razif Gabdoulline, 2005

Back to the index

Privacy Imprint