Dissecting the effects of concentrated carbohydrate solutions on protein diffusion, hydration, and internal dynamics.
We present herein a thorough description of the effects of high glucose concentrations on the diffusion, hydration and internal dynamics of ubiquitin, as predicted from extensive molecular dynamics simulations on several systems described at fully atomistic level. We observe that the protein acts as a seed that speeds up the natural propensity of glucose to cluster at high concentration; the sugar molecules thus aggregate around the protein trapping it inside a dynamic cage. This process extensively dehydrates the protein surface, restricts the motions of the remaining water molecules, and drags the large-scale, collective motions of protein atoms slowing down the rate of exploration of the conformational space despite only a slight dampening of fast, local dynamics. We discuss how these effects could be relevant to the function of sugars as preservation agents in biological materials, and how crowding by small sticky molecules could modulate proteins across different reaction coordinates inside the cellular cytosol.
Laboratory for Biomolecular Modeling, Institute of Bioengineering, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), and Swiss Institute of Bioinformatics (SIB), 1015 Lausanne, Switzerland.
Enrico
E
Spiga
Luciano A
LA
Abriata
Francesco
F
Piazza
Matteo
M
Dal Peraro
D002241:Carbohydrates / Q000737:chemistry*; D004058:Diffusion; D005947:Glucose / Q000737:chemistry / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D025801:Ubiquitin / Q000737:chemistry; D014867:Water / Q000737:chemistry*
D002241:Carbohydrates; D011506:Proteins; D025801:Ubiquitin; D014867:Water; D005947:Glucose