title: Bridging Enzymatic Structure Function via Mechanics: A Coarse-Grain Approach.
abstract: Flexibility is a central aspect of protein function, and ligand binding in enzymes involves a wide range of structural changes, ranging from large-scale domain movements to small loop or side-chain rearrangements. In order to understand how the mechanical properties of enzymes, and the mechanical variations that are induced by ligand binding, relate to enzymatic activity, we carried out coarse-grain Brownian dynamics simulations on a set of enzymes whose structures in the unbound and ligand-bound forms are available in the Protein Data Bank. Our results show that enzymes are remarkably heterogeneous objects from a mechanical point of view and that the local rigidity of individual residues is tightly connected to their part in the protein's overall structure and function. The systematic comparison of the rigidity of enzymes in their unbound and bound forms highlights the fact that small conformational changes can induce large mechanical effects, leading to either more or less flexibility depending on the enzyme's architecture and the location of its ligand-biding site. These mechanical variations target a limited number of specific residues that occupy key locations for enzymatic activity, and our approach thus offers a mean to detect perturbation-sensitive sites in enzymes, where the addition or removal of a few interactions will lead to important changes in the proteins internal dynamics.
authors: Laboratoire de Biochimie Théorique, CNRS UPR9080, Institut de Biologie Physico-Chimique, Paris, France. Electronic address: sacquin@ibpc.fr.
authors: S
authors: S
authors: Sacquin-Mora
mesh_terms: D051229:3-Phosphoshikimate 1-Carboxyvinyltransferase / Q000737:chemistry*; D001665:Binding Sites; D001696:Biomechanical Phenomena; D030562:Databases, Protein; D006867:Hydrolases / Q000737:chemistry*; D007535:Isomerases / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D008025:Ligases / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D013816:Thermodynamics; D014166:Transferases / Q000737:chemistry*
chemical_list: D008024:Ligands; D014166:Transferases; D051229:3-Phosphoshikimate 1-Carboxyvinyltransferase; D006867:Hydrolases; D007535:Isomerases; D008025:Ligases
keywords: Coarse-grain simulations; Enzymes; Ligand binding; Proteins mechanics; Structural change