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Previous studies focusing on overall geometry of protein\u2013protein interfaces, however, concluded that PPI interfaces were generally flat. More recently, this idea has been challenged by their structural and thermodynamic characterisation, suggesting the existence of concave binding sites that are closer in character to traditional small-molecule binding sites, rather than exhibiting complete flatness. Here, we present a large-scale analysis of binding geometry and physicochemical properties of all protein\u2013protein interfaces available in the Protein Data Bank. In this review, we provide a comprehensive overview of the protein\u2013protein interface landscape, including evidence that even for overall larger, more flat interfaces that utilize discontinuous interacting regions, small and potentially druggable pockets are utilized at binding sites.<\/jats:p>","DOI":"10.1093\/bib\/bbac165","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T19:14:56Z","timestamp":1650482096000},"source":"Crossref","is-referenced-by-count":34,"title":["Structural landscapes of PPI interfaces"],"prefix":"10.1093","volume":"23","author":[{"given":"Carlos H M","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Computational Biology and Clinical Informatics, Baker Heart and Diabetes Institute , Melbourne, Victoria"},{"name":"Systems and Computational Biology, Bio21 Institute, University of Melbourne , Melbourne, Victoria"},{"name":"School of Chemistry and Molecular Biosciences, Bio21 Institute, University of Queensland , 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