Determinants of Macromolecular Specificity from Proteomics-Derived Peptide Substrate Data

Abstract

Background: Recent advances in proteomics methodologies allow for high throughput profiling of proteolytic cleavage events. The resulting substrate peptide distributions provide deep insights in the underlying macromolecular recognition events, as determinants of biomolecular specificity identified by proteomics approaches may be compared to structure-based analysis of corresponding protein-protein interfaces.

Method: Here, we present an overview of experimental and computational methodologies and tools applied in the area and provide an outlook beyond the protein class of proteases.

Results and conclusion: We discuss here future potential, synergies and needs of the emerging overlap disciplines of proteomics and structure-based modelling.

Keywords: Macromolecular recognition; molecular modelling; peptide binding; protease substrate profiling; protein-protein-interface; specificity.