Classification of protein protein and protein peptide interactions AI methods for decoding subtle differences for the effective design of biologics

Abstract

Protein-protein interactions (PPI) and protein-peptide interactions (PPepI) are essential for various metabolic, host-defense, and cell-signaling activities. Although both of them fall into the same category of interactions, yet there are subtle differences that exist among them. Peptides and peptidomimetics are promising candidates to modulate PPI as they possess multiple advantages such as long term storage, less prone to degradation, denaturation and aggregation, and flexibility of their optimization, screening and synthesis. When peptide-based mimics are used to strengthen or disrupt protein-protein interactions, understanding these differences is crucial for the design of peptide-based biologics. Many attempts to deploy peptide-based inhibitors in the past did not succeed precisely due to lack of this knowledge. Thus, it is important to comprehend the differences between PPI and PPepI in order to modulate PPI by peptide-based therapeutics. No systematic attempts have been made in the field to classify and differentiate the interactions among these partners. Apart from biologics design, the differentiation and quantification of interactions has multiple applications in computational modelling of protein and peptides.