Mapping Mechanostable Pulling Geometries of Protein-Ligand Complexes

Abstract

ligand binding. We demonstrate the observed differences in the ligand modulation arise due to differences in binding site and binding mode of the two complexes. Our simulations reveal that the transition state structure of SUMO1 gets perturbed on binding with S12. In contrast, the binding of CUE-2 has minimal structural impact of ubiquitin. Thus our study demonstrates that a direct interaction with the b-clamp does not necessarily modulate the mechanical stability of proteins, an observation in contrast with previous studies. Instead ligand binding far from the b-clamp can reinforce the mechanical stability of the proteins. Our study highlights the importance of ligand binding site in modulating mechanical stability of ubiquitin family proteins.