Protein-protein Interfaces Integrated into Interaction Networks: Implications on Drug Design

Gozde      Kar; Guray      Kuzu; Ozlem      Keskin; Attila      Gursoy

Abstract

The growing perception that diseases are often consequences of multiple molecular abnormalities rather than being the result of a single defect highlights the importance of network-centric view in therapeutic approaches. Protein interaction networks may contribute to understanding of disease, assist in drug design and discovery. Here, we review some recent advances in disease-associated protein interaction networks taking a structural approach. We first describe structural aspects of protein-protein interactions and properties of protein interfaces as related to drug design; we address protein interactions in a network perspective; in particular, we illustrate how integrating protein interfaces onto interaction networks can guide the identification of selective drug targets or drugs targeting multiple proteins in a network.

Keywords: Protein-protein interfaces, protein interaction networks, drug design, drug targets, binding site, interfacial residues, transient, amino acid, Glycine, Cystine-Cystine.