Molecular View of Water Dynamics near Model Peptides

Russo, Daniela; Murarka, Rajesh K.; Copley, J. R. D.; Head‐Gordon, Teresa

doi:10.1021/jp051137k

Cited by 124 publications

(148 citation statements)

References 94 publications

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“…Head-Gordon and coworkers have reported heterogeneous water dynamics in the first hydration shell of model peptides (N-acetyl-leucinemethylamide and N-acetyl-glycine-methylamide), with faster water motions near the hydrophobic side chains than near the hydrophilic backbone (45,46). Similar results have been reported for molecular dynamics simulation studies of a folded β-hairpin peptide (30).…”

Section: Discussionsupporting

confidence: 61%

Hydration dynamics at fluorinated protein surfaces

Kwon

Yoo

Othon

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Water-protein interactions dictate many processes crucial to protein function including folding, dynamics, interactions with other biomolecules, and enzymatic catalysis. Here we examine the effect of surface fluorination on water-protein interactions. Modification of designed coiled-coil proteins by incorporation of 5,5,5-trifluoroleucine or (4S)-2-amino-4-methylhexanoic acid enables systematic examination of the effects of side-chain volume and fluorination on solvation dynamics. Using ultrafast fluorescence spectroscopy, we find that fluorinated side chains exert electrostatic drag on neighboring water molecules, slowing water motion at the protein surface.fluorine | noncanonical amino acids | protein engineering | solvation dynamics | ultrafast hydration T he past decade has witnessed substantial expansion in the number and diversity of noncanonical amino acids that can be incorporated into recombinant proteins expressed in bacterial cells (1-3). Fluorinated amino acids have drawn special attention (4-16) because of the unusual solubility properties of fluorinated hydrocarbons. Several independent studies have shown that fluorination of coiled-coil and helix-bundle proteins leads to enhanced stability with respect to thermal or chemical denaturation (6-12), an effect attributed to the hyper-hydrophobic and fluorophilic character of fluorinated amino acid side chains.Although both classes of compounds are hydrophobic, hydrocarbons and fluorocarbons differ in important ways (17)(18)(19)(20)(21)(22). The high electronegativity of fluorine renders the C-F bond both strongly polar and weakly polarizable (17,21,22). The dipole associated with the C-F bond exerts strong inductive effects on neighboring bonds (23) and can form reasonably strong electrostatic interactions with ionic or polar groups when the two moieties are appropriately positioned. The hydrophobic character of fluorinated compounds has been described as "polar hydrophobicity (17)," and is believed to play important roles in organic and medicinal chemistry. Furthermore, the C-F bond is significantly longer than the C-H bond, and the calculated volume of the trifluoromethyl group is about twice that of a methyl group (20). The studies described here constitute an attempt to understand more fully the interaction of water with fluorinated molecular surfaces, and to provide a sound basis for the use of fluorinated amino acids in the engineering of proteins with unique and useful physical properties.The hydration layer adjacent to protein surfaces exhibits properties different from those of bulk water; the more rigid and denser structure of the hydration layer plays a crucial role in protein structure, folding, dynamics, and function (24-26). Elucidation of the dynamic features of this region, on the time scales of atomic and molecular motion, is essential in understanding protein hydration. In the past decade, the knowledge of hydration on protein surfaces has been extensively expanded by studying the dynamic properties of biological water for various pro...

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Section: Discussionsupporting

confidence: 61%

Hydration dynamics at fluorinated protein surfaces

Kwon

Yoo

Othon

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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“…τ j represents the relaxation time of the water molecules in each water phase X j , τ j ∈ τ c , τ p , τ np , τ r . Both experiments [4,19,20,29,30] and theory [1,5,7,9,24] suggest the following hierarchy τ r < τ np < τ p < τ c , where τ r ∼ = 10 −12 s characterizes the mobility of water with no constraints [7,9]; τ np ∼ = 10 −10 s represents the average relaxation time of bulk-like water on the protein surface [4,9,19,20,29,30]; τ p ∼ = 10 −9 is the typical relaxation time of highly structured surface water [4,9,19,20] and τ c > 10 −8 s stands for the relaxation time of immobile water molecules buried in macromolecular structures [1,9,29,30]. From Eq.…”

Section: Resultsmentioning

confidence: 99%

“…Dynamics of water in cells and biological tissues is coupled to the local macromolecular environment [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Therefore, structural alterations of cellular proteins change the distribution and dynamics of surrounding water molecules.…”

Section: Introductionmentioning

confidence: 99%

Hydration Profiles of Amyloidogenic Molecular Structures

et al. 2008

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Hydration shells of normal proteins display regions of highly structured water as well as patches of less structured bulk-like water. Recent studies suggest that isomers with larger surface densities of patches of bulk-like water have an increased propensity to aggregate. These aggregates are toxic to the cellular environment. Hence, the early detection of these toxic deposits is of paramount medical importance. We show that various morphological states of association of such isomers can be differentiated from the normal protein background based on the characteristic partition between bulk, caged, and surface hydration water and the magnetic resonance (MR) signals of this water. We derive simple mathematical equations relating the compartmentalization of water to the local hydration fraction and the packing density of the newly formed molecular assemblies. Then, we employ these equations to predict the MR response of water constrained by protein aggregation. Our results indicate that single units and compact aggregates that contain no water between constituents induce a shift of the MR signal from normal protein background to values in the hyperintensity domain (bright spots), corresponding to bulk water. In contrast, large plaques that cage significant amounts of water between constituents are likely to generate MR responses in the hypointensity domain (dark spots), typical for strongly correlated water. The implication of these results is that amyloids can display both dark and bright spots when compared to the normal gray background tissue on MR images. In addition, our findings predict that the bright spots are more likely to correspond to amyloids in their early stage of development. The results help explain the MR contrast patterns of amyloids and suggest a new approach for identifying unusual protein aggregation related to disease.

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“…31 They found that the hydration layer around the carbohydrate extends up to 5.13 Å from the surface and contains 123 water molecules. 31 In contrast to the large body of work demonstrating ultraslow dynamics near a protein, incoherent quasi-elastic neutron scattering 32,33 and NMRD (nuclear magnetic relaxation dispersion) 34 studies suggest very slight slowing down of the water molecules near a protein. It may be noted that different techniques detect different things.…”

mentioning

confidence: 96%

Ultrafast Dynamics in Biological Systems and in Nano-Confined Environments

Sahu

Mondal

Ghosh

et al. 2007

Bulletin of the Chemical Society of Japan

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Ultrafast chemical dynamics in a nano-confined system is very different from that in a bulk liquid. In this account, we give an overview on recent femtosecond study on dynamics of ultrafast chemical processes in the nanocavity of a biological system. Dynamics in a biological system crucially depends on the location of the fluorescent probe. We show that one can study solvation dynamics in different regions (i.e. spatially resolve) by variation of the excitation wavelength. We discuss two interesting cases of how structure affects dynamics. First, solvation dynamics of two protein folding intermediates of cytochrome c is found to be differ significantly in the ultrafast initial part (<20 ps). Second, methyl substitution of the OH group in a cyclodextrin is shown to slow down the initial part of solvation dynamics quite dramatically. The most interesting observation is the discovery of the ultraslow component of solvation dynamics which is 100-1000 times slower compared to bulk water. The electron-and proton-transfer processes in a nano-confined system are found to be markedly retarded because of slow solvation and structural constraints. Close proximity of the reactants in a confined system is expected to accelerate dynamics of bi-molecular processes. This is illustrated by ultrafast fluorescence resonance energy transfer (FRET) in %1 ps time scale between a donor and an acceptor in a micelle. Finally, it is demonstrated that the decay of fluorescence anisotropy provides structural information (e.g. size of a cyclodextrin inclusion complex) and may be used to detect formation of a nano-aggregate.

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Molecular View of Water Dynamics near Model Peptides

Cited by 124 publications

References 94 publications

Hydration dynamics at fluorinated protein surfaces

Hydration dynamics at fluorinated protein surfaces

Hydration Profiles of Amyloidogenic Molecular Structures

Ultrafast Dynamics in Biological Systems and in Nano-Confined Environments

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