LAUSR

Protein-protein and protein-peptide recognition are among the most important processes that make signal transmission and transduction possible in a cell; they also play a role in cellular processes involving diseases. Theoretical approaches in the study of these processes from a structural and thermodynamic viewpoint have focused on computational methods aimed at modelling, predicting, and characterizing the interface between the interacting proteins. Indeed, computational techniques represent potent tools for understanding PPI mechanisms at the atomic level: this information can then be exploited for designing molecules able to interfere with them. However, designing molecules to directly targeting protein-protein interactions (PPI) is a difficult task. Differently from other computationally driven small molecule discovery efforts, PPI targeting presents unique challenges: high resolution structural information on targets is not easily available or predictable; PPI surfaces deviate from the conventional druggable sites targeted by therapeutic small molecules, being more hydrophobic, shallow and larger, thus having higher degree of conformational freedom. The unique nature of PPI is also reflected by known PPI inhibitors, which tend to have different physicochemical features from typical small compound drugs. In this Research Topic, a few approaches are presented that try to overcome the complexity of designing PPI inhibitors or modulators by providing new computational methods or analysis tools to assist PPI drug discovery, as well as facilitate integration with experimental data. Currently, no computational method can reliably predict the three-dimensional structure of protein complexes. Molecular docking is still an open challenge for proteinprotein interactions, with one of the critical steps being the post-docking processing for determining the correct binding modes among the different models. Ranaudo et al. addressed this problem for affitins, a class of easily engineerable proteins that can be OPEN ACCESS