Protein-Protein Association Reaction Study on GB1 Protein Dimerization in a Crowded Environment

Abstract

Protein associated states are crucial in regulating functions such as DNA binding, immune response, enzymatic reactions, signal transduction. Recent studies indicate that the macromolecular crowders, that occupy 30-40% of the intracellular environment, can significantly favor the formation of protein self-aggregated complexes, whereas some crowders even impart a destabilizing effect on protein-protein complexes. In this work, we investigate dimerization of Immunoglobulin-binding protein G of the B1 domain of the Streptococcus species in presence of lysozyme crowders using Martini coarse-grained model. Simulations are biased with metadynamics and parallel tempering methods to ensure convergence of the free energy of binding. Our analysis shows that dimer formation is destabilized in presence of lysozyme crowders and the domain-swapped dimer of GB1 protein is more likely to be formed in both with and without crowder systems. The findings are compared with available experimental results and the scaled particle theory model.