Unique Physicochemical Patterns of Residues in Protein-Protein Interfaces

Lázár, Tamás and Guharoy, Mainak and Schád, Éva and Tompa, Péter (2018) Unique Physicochemical Patterns of Residues in Protein-Protein Interfaces. JOURNAL OF CHEMICAL INFORMATION AND MODELING, 58 (10). pp. 2164-2173. ISSN 1549-9596

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Protein-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.

Item Type: Article
Additional Information: VIB-VUB Center for Structural Biology, Vlaams Instituut voor Biotechnologie, Pleinlaan 2, Brussels, 1050, Belgium Structural Biology Brussels, Vrije Universiteit Brussel, Pleinlaan 2, Brussels, 1050, Belgium Institute of Enzymology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudosok korutja 2, Budapest, 1117, Hungary Export Date: 9 January 2019 CODEN: JCISD Correspondence Address: Tompa, P.; VIB-VUB Center for Structural Biology, Vlaams Instituut voor Biotechnologie, Pleinlaan 2, Belgium; email: Funding details: Fonds Wetenschappelijk Onderzoek, FWO, PD-OTKA 108772 Funding details: Fonds Wetenschappelijk Onderzoek, FWO, K124670 Funding details: Fonds Wetenschappelijk Onderzoek, FWO, FWO Funding text 1: *E-mail: (P.T.). ORCID Tamas Lazar: 0000-0001-7496-6711 Eva Schad: 0000-0002-3006-2910 Author Contributions P.T., E.S. and T.L. conceived the conceptual framework of the study. M.G. and P.T. designed the computational analysis. T.L. performed the analysis with technical support from M.G. M.G., E.S., and P.T. supervised the analysis. T.L. and P.T. wrote the paper. All authors reviewed the manuscript. Funding This work was supported by the Odysseus Grant G.0029.12 from Research Foundation Flanders (FWO) and OTKA grant K124670 to P.T. and by the OTKA grant PD-OTKA 108772 to E.S. Notes The authors declare no competing financial interest. The source code of iPat and an example of usage demonstrating how the calculations for 3ZIW (shown in Figure S1) can be reproduced are available via GitHub: lazartomi/iPat/.
Subjects: Q Science / természettudomány > QH Natural history / természetrajz > QH301 Biology / biológia > QH3011 Biochemistry / biokémia
Depositing User: MTMT SWORD
Date Deposited: 07 Mar 2019 13:48
Last Modified: 07 Mar 2019 13:48

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