Probing Polar Solvation Dynamics in Proteins:  A Molecular Dynamics Simulation Analysis

Golosov, Andrei A.; Karplus, Martin

doi:10.1021/jp065493u

Cited by 111 publications

(180 citation statements)

References 36 publications

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“…Observation of the fs component suggests that the Trp probe in the test proteins is neither crowded by neighboring residues nor protected from exposure to water (27,28,41). The slowest phase of hydration dynamics (on the time scale of tens of ps) is collective water network rearrangement coupled to protein fluctuation dynamics (27,(41)(42)(43).…”

Section: Resultsmentioning

confidence: 99%

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: Resultsmentioning

confidence: 99%

Hydration dynamics at fluorinated protein surfaces

Kwon

Yoo

Othon

et al. 2010

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

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“…Motivated by these experiments, Golosov and Karplus performed molecular dynamic simulations for this 56 residue protein in a solvent of 6205 water molecules. [105] They calculated the time-dependent correlation function for the electrostatic interaction energy of the site residue with the rest of the system. This quantity should scale with the energy gap correlation function.…”

Section: B Protein Gb1 In Watermentioning

confidence: 99%

Quantum Dynamics of Electronic Excitations in Biomolecular Chromophores: Role of the Protein Environment and Solvent

2008

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We consider continuum dielectric models as minimal models to understand the effect of a surrounding globular protein and solvent on the quantum dynamics of electronic excitations in a biological chromophore. For these models we derive expressions for the frequency dependent spectral density which describes the coupling of the electronic levels in the chromophore to its environment. The magnitude and frequency dependence of the spectral density determines whether or not the quantum dynamics is coherent or incoherent, and thus whether on not one can observe quantum interference effects such as Rabi oscillations. We find the contributions to the spectral density from each component of the chromophore environment: the bulk solvent, protein, and water bound to the protein. The relative importance of each component to the quantum dynamics of the chromophore is determined by the time scale on which one is considering the dynamics. Our results provide a natural explanation and model for the different time scales observed in the spectral density extracted from the solvation dynamics probed by ultra-fast laser spectroscopy techniques such as the dynamic Stokes shift and three pulse photon echo spectroscopy. Our results are used to define under what conditions the dynamics of the excited chromophore is dominated by the surrounding protein and when it is dominated by dielectric fluctuations in the solvent. We show that even when the chromophore is shielded from the solvent by the protein ultra-fast solvation can be dominated by the solvent. Hence, we suggest that the ultra-fast solvation recently seen in some biological chromophores should not necessarily be assigned to ultra-fast protein dynamics. The magnitudes of the spectral density that we estimate from our continuum models and extracted from experiment suggest that most quantum dynamics of electronic excitations is incoherent. A possible exception is transfer of excitons between neigbouring chromophores in photosynthetic systems.

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“…6,[9][10][11] Simultaneously there are some other works, using experimental techniques and computer simulations, which report a wide range of time scales for the dynamics of water around biomolecules from femto-to nanoseconds (10 -15 to 10 -9 s). In particular, they describe a slow component of the solvation dynamics on the 100-1000 picoseconds time scale.…”

Section: Introductionmentioning

confidence: 99%

Water dynamics on the surface of the protein barstar

Moron

2012

Phys. Chem. Chem. Phys.

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Water plays a fundamental function in life and technology. To gain a deeper knowledge to the problem of the hydration of biomolecules, the dynamics of water around a 89-residue protein of interest in molecular recognition, cancer cell research and amyloid fribrils investigations is analyzed. The biomolecule is the ribonuclease inhibitor barstar wild-type. The dynamics of the protein and the 7430 water molecules of the bath in which is immersed, is monitored during a period of 7 ns by using all-atom molecular dynamics simulations. The results confirm the existence of multiple time scales in the dynamics of water (10 -1 to 10 3 ps) at atomic level. That heterogeneity of residence times is not lost if the system of reference is just one atom of the inhibitor. The dehydration process of barstar is considered through the analysis of time correlation functions obtaining an averaged decay time of τ = 84.0 ± 0.3 ps. A power law distribution, with scaling exponent α = 0.57 ± 0.04, suggests that this hydration water exhibits a scale free dynamics (with respect to the residence time of solvent molecules). Most of the water molecules located on the surface of the protein spend times smaller than the picosecond while only about 1% of them stay for periods of time on the nanosecond scale.

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Probing Polar Solvation Dynamics in Proteins: A Molecular Dynamics Simulation Analysis

Cited by 111 publications

References 36 publications

Hydration dynamics at fluorinated protein surfaces

Hydration dynamics at fluorinated protein surfaces

Quantum Dynamics of Electronic Excitations in Biomolecular Chromophores: Role of the Protein Environment and Solvent

Water dynamics on the surface of the protein barstar

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