ci8b00270_si_001.pdf (1.1 MB)
Unique Physicochemical Patterns of Residues in Protein–Protein Interfaces
journal contribution
posted on 2018-09-13, 00:00 authored by Tamas Lazar, Mainak Guharoy, Eva Schad, Peter TompaProtein–protein
interactions can be characterized by high-resolution structures of
complexes, from which diverse features of the interfaces can be derived.
For the majority of protein–protein interactions identified,
however, there is no information on the structure of the complex or
the interface involved in the interaction. Understanding what surface
properties drive certain interactions is crucial in the functional
evaluation of protein complexes. Here we show that the local patterning
of the physicochemical properties of amino acids within surface patches
is characteristic of interfaces. To describe this feature in a quantitative
manner, we have defined a statistical potential, iPat, as a measure
of surface patterning. iPat, which does not take evolutionary conservation
or knowledge of the interaction partner into consideration, represents
a function principally different from algorithms that consider intermolecular
contacts. We assess its suitability for characterizing protein and
peptide interfaces, and we demonstrate that iPat is uniquely descriptive
for interfaces of proteins that undergo large conformational changes
or that are involved in the binding of intrinsically disordered protein
(IDP) partners. We suggest that as a stand-alone propensity or in
combination with other features, iPat represents a new feature in
analyzing the functional binding specificity of protein–protein
interactions that has better predictive potential than other simple
1D features, such as hydrophobicity or stickiness.