title: The conformational free energy landscape of beta-D-glucopyranose. Implications for substrate preactivation in beta-glucoside hydrolases.
abstract: Using ab initio metadynamics we have computed the conformational free energy landscape of beta-D-glucopyranose as a function of the puckering coordinates. We show that the correspondence between the free energy and the Stoddard's pseudorotational itinerary for the system is rather poor. The number of free energy minima (9) is smaller than the number of ideal structures (13). Moreover, only six minima correspond to a canonical conformation. The structural features, the electronic properties, and the relative stability of the predicted conformers permit the rationalization of the occurrence of distorted sugar conformations in all the available X-ray structures of beta-glucoside hydrolase Michaelis complexes. We show that these enzymes recognize the most stable distorted conformers of the isolated substrate and at the same time the ones better prepared for catalysis in terms of bond elongation/shrinking and charge distribution. This suggests that the factors governing the distortions present in these complexes are largely dictated by the intrinsic properties of a single glucose unit.
authors: Centre especial de Recerca en Química Teorica, Parc Científic de Barcelona, Josep Samitier 1-5, 08028 Barcelona, Spain.
authors: Xevi
authors: X
authors: Biarnés
authors: Albert
authors: A
authors: Ardèvol
authors: Antoni
authors: A
authors: Planas
authors: Carme
authors: C
authors: Rovira
authors: Alessandro
authors: A
authors: Laio
authors: Michele
authors: M
authors: Parrinello
mesh_terms: D002236:Carbohydrate Conformation; D003198:Computer Simulation; D005947:Glucose / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000737:chemistry* / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D006026:Glycoside Hydrolases; D005947:Glucose