TY - JOUR

T1 - Understanding Protein-Protein Interactions Using Local Structural Features

AU - Planas-Iglesias, Joan

AU - Bonet, Jaume

AU - García-García, Javier

AU - Marín-López, Manuel A

AU - Feliu, Elisenda

AU - Oliva, Baldo

N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.

PY - 2013/1/23

Y1 - 2013/1/23

N2 - Protein-protein interactions (PPIs) play a relevant role among the different functions of a cell. Identifying the PPI network of a given organism (interactome) is useful to shed light on the key molecular mechanisms within a biological system. In this work, we show the role of structural features (loops and domains) to comprehend the molecular mechanisms of PPIs. A paradox in protein-protein binding is to explain how the unbound proteins of a binary complex recognize each other among a large population within a cell and how they find their best docking interface in a short timescale. We use interacting and non-interacting protein pairs to classify the structural features that sustain the binding (or non-binding) behavior. Our study indicates that not only the interacting region but also the rest of the protein surface are important for the interaction fate. The interpretation of this classification suggests that the balance between favoring and disfavoring structural features determines if a pair of proteins interacts or not. Our results are in agreement with previous works and support the funnel-like intermolecular energy landscape theory that explains PPIs. We have used these features to score the likelihood of the interaction between two proteins and to develop a method for the prediction of PPIs. We have tested our method on several sets with unbalanced ratios of interactions and non-interactions to simulate real conditions, obtaining accuracies higher than 25% in the most unfavorable circumstances.

AB - Protein-protein interactions (PPIs) play a relevant role among the different functions of a cell. Identifying the PPI network of a given organism (interactome) is useful to shed light on the key molecular mechanisms within a biological system. In this work, we show the role of structural features (loops and domains) to comprehend the molecular mechanisms of PPIs. A paradox in protein-protein binding is to explain how the unbound proteins of a binary complex recognize each other among a large population within a cell and how they find their best docking interface in a short timescale. We use interacting and non-interacting protein pairs to classify the structural features that sustain the binding (or non-binding) behavior. Our study indicates that not only the interacting region but also the rest of the protein surface are important for the interaction fate. The interpretation of this classification suggests that the balance between favoring and disfavoring structural features determines if a pair of proteins interacts or not. Our results are in agreement with previous works and support the funnel-like intermolecular energy landscape theory that explains PPIs. We have used these features to score the likelihood of the interaction between two proteins and to develop a method for the prediction of PPIs. We have tested our method on several sets with unbalanced ratios of interactions and non-interactions to simulate real conditions, obtaining accuracies higher than 25% in the most unfavorable circumstances.

U2 - 10.1016/j.jmb.2013.01.014

DO - 10.1016/j.jmb.2013.01.014

M3 - Journal article

C2 - 23353828

VL - 425

SP - 1210

EP - 1224

JO - Journal of Molecular Biology

JF - Journal of Molecular Biology

SN - 0022-2836

IS - 7

ER -