title: Dynamics of Hydration Water around Native and Misfolded α-Lactalbumin.
abstract: As water is an essential ingredient in protein structure, dynamics, and functioning, knowledge of its behavior near proteins is crucial. We investigate water dynamics around bovine α-lactalbumin by combining molecular dynamics simulations with polarization-resolved femtosecond infrared (fs-IR) spectroscopy. We identify slowly reorienting surface waters and establish their hydrogen-bond lifetime and reorientation dynamics, which we compare to the experimentally measured anisotropy decay. The calculated number of slow surface waters is in reasonable agreement with the results of fs-IR experiments. While surface waters form fewer hydrogen bonds than the bulk, within the hydration layer water is slower when donating more hydrogen bonds. At concave sites the protein-water hydrogen bonds break preferably via translational diffusion rather than via a hydrogen-bond jump mechanism. Water molecules reorient slower near these sites than at convex water-exposed sites. Protein misfolding leads to an increased exposure of hydrophobic groups, inducing relatively faster surface water dynamics. Nevertheless, the larger exposed surface slows down a larger amount of water. While for native proteins hydrating water is slower near hydrophobic than near hydrophilic residues, mainly due to stronger confinement, misfolding causes hydrophobic water to reorient relatively faster because exposure of hydrophobic groups destroys concave protein cavities with a large excluded volume.
authors.affiliation: Van't Hoff Institute for Molecular Sciences, Universiteit van Amsterdam , Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: Z F
authors.initials: ZF
authors.lastname: Brotzakis
authors.affiliation: FOM Institute AMOLF , Science Park 104, 1098 XG Amsterdam, The Netherlands.
authors.forename: C C M
authors.initials: CC
authors.lastname: Groot
authors.affiliation: Van't Hoff Institute for Molecular Sciences, Universiteit van Amsterdam , Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: W H
authors.initials: WH
authors.lastname: Brandeburgo
authors.affiliation: FOM Institute AMOLF , Science Park 104, 1098 XG Amsterdam, The Netherlands.
authors.forename: H J
authors.initials: HJ
authors.lastname: Bakker
authors.affiliation: Van't Hoff Institute for Molecular Sciences, Universiteit van Amsterdam , Science Park 904, 1098 XH Amsterdam, The Netherlands.
authors.forename: P G
authors.initials: PG
authors.lastname: Bolhuis
mesh_terms: D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007768:Lactalbumin / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D017510:Protein Folding; D013055:Spectrophotometry, Infrared; D014867:Water / Q000737:chemistry* / Q000378:metabolism
chemical_list: D014867:Water; D007768:Lactalbumin