Computational analyses of the surface properties of protein–protein interfaces

Abstract

Several potential applications of structural biology depend on discovering how one macromolecule might recognize a partner. Experiment remains the best way to answer this question, but computational tools can contribute where this fails. In such cases, structures may be studied to identify patches of exposed residues that have properties common to interaction surfaces and the locations of these patches can serve as the basis for further modelling or for further experimentation. To date, interaction surfaces have been proposed on the basis of unusual physical properties, unusual propensities for particular amino-acid types or an unusually high level of sequence conservation. Using the CXXSurface toolkit, developed as a part of the CCP4MG program, a suite of tools to analyse the properties of surfaces and their interfaces in complexes has been prepared and applied. These tools have enabled the rapid analysis of known complexes to evaluate the distribution of (i) hydrophobicity, (ii) electrostatic complementarity and (iii) sequence conservation in authentic complexes, so as to assess the extent to which these properties may be useful indicators of probable biological function.

An interaction between the methyltransferase and RNA dependent RNA polymerase domains of the West Nile virus NS5 protein

“…Surface exposed residues have been shown to be critical for the interaction between proteins (Gruber et al, 2007). To further identify contact sites between the NS5 domains, single, double and triple mutants were generated in the aA3-motif region of the recombinant MTase and assessed for the importance of these residues in the interaction with recombinant POL.…”

Mutations that Alter RcdA Surface Residues Decouple Protein Localization and CtrA Proteolysis in Caulobacter crescentus

“…Because surface-exposed hydrophobic residues are often involved in protein-protein interactions, 26 we replaced the conserved residues L61 and A64 (Fig. 1c, left) with the polar amino acid serine to create RcdA-patch-GFP.…”

Crystal Structure of BamB from Pseudomonas aeruginosa and Functional Evaluation of Its Conserved Structural Features

“…However, the top of the propeller displays grooves lined with hydrophobic residues (Figure 2C) that alternate with grooves rich in charged residues (Figure 2B). Surfaces involved in protein-protein interactions are more hydrophobic than exposed surfaces [37]. Therefore, the grooves lined with hydrophobic residues on the top surface of BamB may represent sites of interaction with other BAM components, assembly chaperones or nascent OMPs.…”