PRODIGY: A Contact-based Predictor of Binding Affinity in Protein-protein Complexes

Abstract

Biomolecular interactions between proteins regulate and control almost every biological process in the cell. Understanding these interactions is therefore a crucial step in the investigation of biological systems and in drug design. Many efforts have been devoted to unraveling principles of protein-protein interactions. Recently, we introduced a simple but robust descriptor of binding affinity based only on structural properties of a protein-protein complex. In Vangone and Bonvin (2015), we demonstrated that the number of interfacial contacts at the interface of a protein-protein complex correlates with the experimental binding affinity. Our findings have led one of the best performing predictor so far reported (Pearson's Correlation r = 0.73; RMSE = 1.89 kcal mol^-1). Despite the importance of the topic, there is surprisingly only a limited number of online tools for fast and easy prediction of binding affinity. For this reason, we implemented our predictor into the user-friendly PRODIGY web-server. In this protocol, we explain the use of the PRODIGY web-server to predict the affinity of a protein-protein complex from its three-dimensional structure. The PRODIGY server is freely available at: http://milou.science.uu.nl/services/PRODIGY.

Keywords: Kd; Buried surface area; PPIs; Prediction; Protein contacts; Protein interface; Protein-protein interactions; Web-server.

Figure 1.. Example view of an input page of the PRODIGY web-server.

(http://milou.science.uu.nl/services/PRODIGY)

Figure 2.. A three-dimensional representation of the complex 1E6J with the color-coding of the PRODIGY script (.pml).

This script can be downloaded from the PRODIGY output page. Interactor 1 is shown in light pink (chains L and H in this example) and Interactor 2 in light blue (chain P), respectively. The interacting residues are represented in sticks in blue and dark pink for Interactor 1 and Interactor 2, respectively.