Proteins carry out their diverse functions in cells by forming interactions with each other. The dynamics of these interactions are quantified by the measurement of association and dissociation rate constants. Relative to the efforts made to model the association of biomolecules, little has been studied to understand the principles of protein complex dissociation. Using the interaction between colicin E9 endonucleases and immunity proteins as a test system, here we develop a coarse-grained simulation method to explore the dissociation mechanisms of protein complexes. The interactions between proteins in the complex are described by the knowledge-based potential that was constructed by the statistics from available protein complexes in the structural database. Our study provides the supportive evidences to the dual recognition mechanism for the specificity of binding between E9 DNase and immunity proteins, in which the conserved residues of helix III of Im2 and Im9 proteins act as the anchor for binding, while the sequence variations in helix II make positive or negative contributions to specificity. Beyond that, we further suggest that this binding specificity is rooted in the process of complex dissociation instead of association. While we increased the flexibility of protein complexes, we further found that they are less prone to dissociation, suggesting that conformational fluctuations of protein complexes play important functional roles in regulating their binding and dissociation. Our studies therefore bring new insights to the molecule mechanisms of protein-protein interactions, while the method can serve as a new addition to a suite of existing computational tools for the simulations of protein complexes.
ASJC Scopus subject areas
- General Physics and Astronomy
- Physical and Theoretical Chemistry