TY - JOUR T1 - The Modular Organization of Domain Structures: Insights into Protein–Protein Binding A1 - del Sol, Antonio A1 - Carbonell, Pablo Y1 - 2007/12/07 N2 - Author SummaryProteins are built by domains, which mediate protein–protein interactions involved in different biological activities. A challenging problem in computational biology is the understanding of the domain–domain interaction mechanism. Here, we propose a new approach for the analysis and prediction of domain–domain binding sites. Our computational approach, which relies on the modular division of 3-D domain structures, identifies modular regions involved in binding and can complement previously introduced predictive methods. Further results illustrate that binding sites display a modular configuration. A detailed analysis of protein domains with available experimental binding data revealed that modules are energetically independent from each other, whereas residues within modules contribute cooperatively to the binding energy. The modular composition of binding surfaces may generate high binding affinity and specificity, and facilitate the appearance of new domain binding partners. This advantageous organization of protein structures has been conserved by evolution and may be used to design an effective drug strategy. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 3 IS - 12 UR - https://doi.org/10.1371/journal.pcbi.0030239 SP - e239 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.0030239 ER -