title: All-atom simulations of crowding effects on ubiquitin dynamics.
abstract: It is well-known that crowded environments affect the stability of proteins, with strong biological and biotechnological implications; however, beyond this, crowding is also expected to affect the dynamic properties of proteins, an idea that is hard to probe experimentally. Here we report on a simulation study aimed at evaluating the effects of crowding on internal protein dynamics, based on fully all-atom descriptions of the protein, the solvent and the crowder. Our model system consists of ubiquitin, a protein whose dynamic features are closely related to its ability to bind to multiple partners, in a 325 g L⁻¹ solution of glucose in water, a condition widely employed in in vitro studies of crowding effects. We observe a slight reduction in loop flexibility accompanied by a dramatic restriction of the conformational space explored in the timescale of the simulations (∼0.5 µs), indicating that crowding slows down collective motions and the rate of exploration of the conformational space. This effect is attributed to the extensive and long-lasting interactions observed between protein residues and glucose molecules throughout the entire protein surface. Potential implications of the observed effects are discussed.
authors.affiliation: Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique F´ed´erale de Lausanne-EPFL, Lausanne, Switzerland.
authors.forename: Luciano A
authors.initials: LA
authors.lastname: Abriata
authors.forename: Enrico
authors.initials: E
authors.lastname: Spiga
authors.forename: Matteo
authors.initials: M
authors.lastname: Dal Peraro
mesh_terms: D018360:Crystallography, X-Ray; D005947:Glucose / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D025341:Principal Component Analysis; D011485:Protein Binding; D011487:Protein Conformation; D012997:Solvents / Q000737:chemistry; D025801:Ubiquitin / Q000737:chemistry*; D014867:Water / Q000737:chemistry
chemical_list: D012997:Solvents; D025801:Ubiquitin; D014867:Water; D005947:Glucose