Structural Prediction of Protein–Protein Interactions by Docking: Application to Biomedical Problems [chapter]

Didier Barradas-Bautista, Mireia Rosell, Chiara Pallara, Juan Fernández-Recio
2018 Advances in Protein Chemistry and Structural Biology  
A huge amount of genetic information is available thanks to the recent advances in sequencing technologies and the larger computational capabilities, but the interpretation of such genetic data at phenotypic level remains elusive. One of the reasons is that proteins are not acting alone, but are specifically interacting with other proteins and biomolecules, forming intricate interaction networks that are essential for the majority of cell processes and pathological conditions. Thus,
more » ... ng such interaction networks is an important step in understanding how information flows from gene to phenotype. Indeed, structural characterization of protein-protein interactions at atomic resolution has many applications in biomedicine, from diagnosis and vaccine design, to drug discovery. However, despite the advances of experimental structural determination, the number of interactions for which there is available structural data is still very small. In this context, a complementary approach is computational modeling of protein interactions by docking, which is usually composed of two major phases: i) sampling of the possible binding modes between the interacting molecules, and ii) scoring for the identification of the correct orientations. In addition, prediction of interface and hot-spot residues is very useful in order to guide and interpret mutagenesis experiments, as well as to understand functional and mechanistic aspects of the interaction. Computational docking is already being applied to specific biomedical problems within the context of personalized medicine, for instance, helping to interpret pathological mutations involved in protein-protein interactions, or providing modeled structural data for drug discovery targeting protein-protein interactions. PROTEIN-PROTEIN DOCKING IN BIOMEDICINE 3 Keywords: Protein-protein interactions, complex structure, computational docking, interface prediction, hot-spot residues, drug discovery, edgetic effect, pathological mutations.
doi:10.1016/bs.apcsb.2017.06.003 pmid:29412997 fatcat:6dsojxsybrfrthdz3yhlqmplxu