Skip to Main content Skip to Navigation
Journal articles

Great interactions: How binding incorrect partners can teach us about protein recognition and function

Abstract : Protein–protein interactions play a key part in most biological processes and understanding their mechanism is a fundamental problem leading to numerous practical applications. The prediction of protein binding sites in particular is of paramount importance since proteins now represent a major class of therapeutic targets. Amongst others methods, docking simulations between two proteins known to interact can be a useful tool for the prediction of likely binding patches on a protein surface. From the analysis of the protein interfaces generated by a massive cross-docking experiment using the 168 proteins of the Docking Benchmark 2.0, where all possible protein pairs, and not only experimental ones, have been docked together, we show that it is also possible to predict a protein's binding residues without having any prior knowledge regarding its potential interaction partners. Evaluating the performance of cross-docking predictions using the area under the specificity-sensitivity ROC curve (AUC) leads to an AUC value of 0.77 for the complete benchmark (compared to the 0.5 AUC value obtained for random predictions). Furthermore, a new clustering analysis performed on the binding patches that are scattered on the protein surface show that their distribution and growth will depend on the protein's functional group. Finally, in several cases, the binding-site predictions resulting from the cross-docking simulations will lead to the identification of an alternate interface, which corresponds to the interaction with a biomolecular partner that is not included in the original benchmark.
Document type :
Journal articles
Complete list of metadata

Cited literature [75 references]  Display  Hide  Download

https://hal.sorbonne-universite.fr/hal-01347160
Contributor : Gestionnaire HAL-UPMC Connect in order to contact the contributor
Submitted on : Wednesday, July 20, 2016 - 2:46:46 PM
Last modification on : Tuesday, February 8, 2022 - 3:32:07 AM

File

prot25086-1.pdf
Publication funded by an institution

Licence


Distributed under a Creative Commons Attribution - NonCommercial - NoDerivatives 4.0 International License

Identifiers

Citation

Lydie Vamparys, Benoist Laurent, Alessandra Carbone, Sophie Sacquin-Mora. Great interactions: How binding incorrect partners can teach us about protein recognition and function. Proteins - Structure, Function and Bioinformatics, Wiley, 2016, 84 (10), pp.1408-1421 ⟨10.1002/prot.25086⟩. ⟨hal-01347160⟩

Share

Metrics

Record views

176

Files downloads

148