Structural deformation upon protein-protein interaction: A structural alphabet approach

In this study, we explore the induced fit modifications on a set of 124 proteins available in both bound and unbound forms, in terms of local structure. The local structure is described thanks to a structural alphabet of 27 structural letters that allows a detailed description of the backbone. Using a control set to distinguish induced fit from experimental error and natural protein flexibility, we show that the fraction of structural letters modified upon binding is significantly greater than in the control set (36% versus 28%). This proportion is even greater in the interface regions (41%). Interface regions preferentially involve coils. Our analysis further reveals that some structural letters in coil are not favored in the interface. We show that certain structural letters in coil are particularly subject to modifications at the interface, and that the severity of structural change also varies. These information are used to derive a structural letter substitution matrix that summarizes the local structural changes observed in our data set. We also illustrate the usefulness of our approach to identify common binding motifs in unrelated proteins.Our study provides qualitative information about induced fit. These results could be of help for flexible docking.Most of biochemical reactions inherent to the life of a cell are mediated by protein-protein interactions, e. g. the recognition of a substrate by an enzyme, or an antigen by an antibody. Protein-protein interaction is influenced by several factors like the size and shape of the interface, shape complementarity between interacting proteins or hydrophobicity [1,2]. Interfaces between interacting proteins have been extensively studied for decades now [3,4]. It has been shown that they have distinct features when compared to non-specific interfaces observed in protein crystals [5-9], or when compared to the rest of the protein surface [10-16]. Different models have been proposed for the protein binding process. Th