The glassy state of crambin and the THz time scale protein-solvent fluctuations possibly related to protein function
© Woods; licensee BioMed Central Ltd. 2014
Received: 12 February 2014
Accepted: 4 August 2014
Published: 16 August 2014
THz experiments have been used to characterize the picosecond time scale fluctuations taking place in the model, globular protein crambin.
Using both hydration and temperature as an experimental parameter, we have identified collective fluctuations (<= 200 cm−1) in the protein. Observation of the protein dynamics in the THz spectrum from both below and above the glass transition temperature (Tg) has provided unique insight into the microscopic interactions and modes that permit the solvent to effectively couple to the protein thermal fluctuations.
Our findings suggest that the solvent dynamics on the picosecond time scale not only contribute to protein flexibility but may also delineate the types of fluctuations that are able to form within the protein structure.
KeywordsTHz spectroscopy Protein dynamics Picosecond time scale protein fluctuations Protein glass transition
Proteins are essential components of all living organisms. It has long been recognized from both experimental and theoretical studies that substantial structural fluctuations occur in proteins. And consequently, these fluctuations are in some way essential for biological activity. Crambin is a highly hydrophobic and water insoluble protein, consisting of only 46 amino acids . It occurs in the seeds of the plant Crambe abyssinica and belongs to the thionin family of membrane-active plant toxins. The role of the protein is still largely unknown, although it has been shown to exhibit extensive sequence homology with a family of membrane-active plant toxins . For the most part, the residues in crambin have not been linked to a specific chemical activity, thus this may suggest that its natural function is determined for the most part by its structure, shape, or surface properties.
The crystal structure of crambin has been resolved ,, but only recently at an exceptionally high resolution , (0.48 A). In addition, extensive Neutron diffraction  and NMR studies ,, in conjunction with theoretical investigations, have contributed significantly to the structural foundation of crambin. For this reason crambin is widely used as a model for protein computational studies as well as for the development of methodology used for assessing protein structure . Likewise, the dynamical properties of crambin have also been a focal point of interest. One of the more intriguing aspects of crambin dynamics is the nature of the glass transition that occurs at about 200 K (−73 C). Many proteins and other amorphous solids have been found to undergo this transition, and its presence has been linked with the loss of large-scale collective motions of bonded and non-bonded groups of atoms in the system . In proteins the change in dynamics that occurs during the transition has been particularly intriguing because the internal motions that are affected are often those that have been conjectured to be important for protein function -–. For instance, the large-scale collective motions in proteins are often viewed as transitions from one distinct protein conformational state to another and typically occur on fairly long time scales ranging from milliseconds to seconds. While the fast fluctuations within or between a specific protein conformation take place on a much shorter time scale (femtoseconds to picoseconds) and act as preliminary steps that guide the longer time scale conformational changes. These fast, thermal fluctuations in proteins would be visible in the THz region of the spectrum. Furthermore, there appears to be a growing number of studies ,-– that have unequivocally demonstrated that the solvent is in some way intrinsically coupled with the fast dynamics of some proteins that are activated during the transition.
One question that we would like to begin to contemplate through the work presented in this manuscript is the type of distinctive information that can be obtained from THz time scale measurements on relevant protein motions that arise during the onset of the protein glass transition; and consequently, their contribution to overall protein function? At this point, we are certainly in no position to answer this question on a comprehensive level, but we can begin to address this query in a limited manner by considering the response of the model protein to both temperature and its immediate surroundings as it progresses through this dynamical transition. It is widely accepted that protein picosecond time scale fluctuations below 200 K are mostly harmonic in nature ,,, and under this premise, only able to explore a limited portion of the protein conformational landscape that maps out protein function ,. However, once the (glass) transition temperature has been reached, the protein atoms begin to vibrate anharmonically and they are no longer confined to a restricted topography. Incidentally, the anharmonic fluctuations that develop within the protein are assumed to be greatly enhanced through interaction with the protein solvent ,-–. To comprehend both the nature and origin of the detected modes in the THz spectrum of crambin, we have carried out experiments that chart the evolution of the protein fluctuations as the glass transition is crossed as both a function of temperature and hydration. In this case, the amount of solvent in the hydration shell is used as an experimental variable to assess how the picosecond time scale fluctuations arising in the hydration layer may couple to the relaxational degrees of freedom of the protein during the onset of the transition. And although the internal fluctuations of the protein are explored experimentally, in this investigation we also include a computational component to our analysis (by way of molecular dynamic (MD) simulation) to aid in the experimental interpretation of the detected modes. Our aim is to provide a clearer picture about the molecular mechanism of the actual transition in a model protein system and perhaps a backstory about the possible role that these motions play in protein function.
Results and discussion
The glass transition in crambin and protein intrinsic modes
From the MD simulations performed in our analysis of crambin, we have determined that the surface residues in the turn regions of the protein have the largest amplitude dynamics in the THz region of the simulation spectrum. And additionally, the actual number of solvent molecules in the hydration layer also appears to have a strong influence on both the amplitude and the vibrational frequency of the protein fluctuations that arise due to contact with the surrounding water molecules. For this reason, in this investigation we have prepared two distinct samples of crambin with differing number of water molecules within the hydration shell. Our objective for the preparation of the individual samples is to observe how solvent coupling may affect the instrinic dynamics of a globular protein on the picosecond time scale. In one sample, there are only an adequate number of water molecules to fill the first or primary layer of the hydration shell. The other sample possesses a greater number of water molecules such that there are a sufficient number to completely fill both the first and the second hydration layer within the shell. From this point on, the samples will now appropriately be referred to as the low hydration sample (LHS) and the high hydration sample (HHS) for the remainder of the manuscript.
Moreover, we have prepared equivalent samples for the MD simulations carried out in this investigation. In the simulations, the hydration layer of the low hydration crambin sample contains water molecules to within a 3.8 Å distance from the protein surface, which is also consistent with the minimum number of water molecules that have been found to be necessary for hydrating both polar and apolar amino acid surface groups in the primary hydration layer of proteins . It also corresponds with the estimated number of water molecules in the hydration shell of our experimentally prepared low hydration crambin sample. The higher hydration sample from the MD simulation contains water molecules that extend out to 8.0 Å distance from the protein surface. The higher hydration MD simulation sample of crambin also approximates the measured number of water molecules in the analogous experimental sample and has been shown to relate to a biologically relevant hydration level  in other globular proteins. Although, it is important to note that recent experimental evidences suggests that the hydration layer around a protein has dynamics distinct from the bulk water that extends as far as 10 Å from the protein surface  with the effects on the surrounding water network reaching beyond a distance of 20 Å  from the protein periphery.
Hydrogen-bonding (H-bonding) fluctuations investigated from MD simulation
Probing protein-protein H-bonding fluctuations in the low frequency spectral region from MD simulation
Probing solvent-protein H-bonding fluctuations in the low frequency spectral region from MD simulation
Interestingly, analyzing the role of solvent coupling to the low-frequency protein dynamics from the MD simulation (Figure 2b), we also find differences when contrasting the two different hydrated crambin samples. In Figure 2b, it becomes apparent that the LHS crambin interaction with the solvent molecules in the hydration shell is more pronounced when compared with that of the HHS. Specifically, protein-solvent interactions create a prominent translational peak at 25 cm−1 in the LHS while comparable solvent-induced fluctuations in HHS are generally revealed to be much weaker.
Deuterium exchange and the effect of solvent dynamics on the experimentally detected THz time scale protein global modes
Velocity autocorrelation function from MD simulation and its relationship to experimentally detected low-frequency global modes in crambin
Low frequency collective excitations in the interfacial hydration water of crambin identified from MD simulation
Experimental detection of THz translational modes in crambin hydration water
In Figure 6a, the HHS in the water translational region that we detect experimentally has a narrow, prominent band centered at about 225 cm−1 that initially grows in intensity as the temperature is increased but broadens and loses intensity at ambient temperature. Interestingly, the other two prominent peaks centered at approximately 205 cm−1 and 185 cm−1 in the HHS experimental spectra are somewhat temperature independent and do not change appreciably as the temperature is varied. Incidentally, on closer inspection, the band located close to 205 cm−1 in the HHS spectra appears to be comprised of a cluster of peaks rather than a single individual peak. The cluster includes peaks at approximately 195 cm−1, 202 cm−1, and 207 cm−1. The varied temperature dependency of the individual peaks in the cluster suggests that the bands may be composed of a mixture of water structures with differing levels of H-bond connectivity. It is interesting to note that cluster vibrations involving combinations of O-H●●● O stretching vibrations have been detected in both theoretical  and experimental  investigations in liquid water at around 200 cm−1.
The experimentally detected water translational bands in the LHS in Figure 6b feature peaks at a similar frequency when contrasted with the HHS but the temperature progression differs significantly. The intensity of the 225 cm−1 band is greatly reduced in the LHS. There is a minor change in peak intensity as the temperature is increased but at room temperature the band has almost completely disappeared from the spectrum. Intriguingly, both the 205 cm−1 and 185 cm−1 modes have very notable temperature dependencies in the LHS spectra. The 205 cm−1 dominates the spectrum at 93 K while there is only a shoulder at 185 cm−1. As the temperature is increased the peak at 205 cm−1 decreases in intensity whereas the 185 cm−1 grows in intensity and shifts to a slightly lower frequency. The singly resolved band at 205 cm−1 (rather than a cluster of vibrational modes) and its clear temperature dependency may indicate that the hydration shell in the LHS is comprised of a more uniform population of O-H●●●O stretching vibrations in general. However, since the nature of the mode(s) close to 205 cm−1 is presently uncertain in both crambin samples we will focus our efforts on trying to elucidate the characteristics of the 225 cm−1 and 185 cm−1 modes in the experimental translation region. Under this premise, we will assume that both the 225 cm−1 and 185 cm−1 modes are directly related to distinct water structures in the protein solvent shell. In this context, the experimental spectra suggest that in the HHS solvent there are a far greater number of water molecules arranged in a tetrahedral configuration at low temperature but under ambient conditions the number of water molecules in both “structured” and “distorted” H-bond configurations is almost equal. On the other hand, the LHS hydration shell is almost entirely comprised of unstructured water molecules above 200 K and further, the motion associated with these molecules in the shell appears to be anharmonic.
Interestingly, in both samples in Figure 6, the peak at ~ 225 cm−1 has a maximum amplitude at 200 K but at all temperatures investigated there is no shift in peak frequency suggesting that the fluctuation remains vibrational for all temperatures explored. We see a similar trend with the peak intensity at 185 cm−1 at 200 K in the LHS sample in Figure 6b, only in this case there is a clear red-shift of the peak frequency as the temperature is increased above 200 K, implying that the motion associated with the fluctuation is anharmonic . Previous work on myoglobin using both experimental and computational simulations ,, have detected a dynamical transition above 180 K in the protein that results from a coupling of fast (picosecond time scale) local motions in the protein with slower, collective protein fluctuations. This coupling of motions is strongly interconnected with a glass-like transition that takes place in the protein hydration shell. Further, the picosecond time scale structural fluctuations in the protein that are activated during the transition are anharmonic in nature. Using these previous investigations on protein-solvent dynamics as a basis for a description of what we observe in our experimental studies on crambin, it is conceivable that the motion associated with the less structured water molecules in the LHS solvent spectrum in Figure 6b is directly tied with the long-range communication that we have detected experimentally in the protein under low hydration conditions (Figures 1 and 3). Under this premise, we speculate that the anharmonic dynamics of the solvent molecules within the hydration shell couple with protein motions and promote long-range coherence in the protein three-dimensional structure. In the HHS there seems to be an entirely different mechanism fostering water molecule intermolecular associations in the hydration shell. Based on the characteristics of the detected translation modes in Figure 6a, the motion of water molecules in the HHS hydration shell is dominated by more self-associating, localized dynamics that is not readily integrated into the relaxational processes of the protein. Feasibly this then begins to provide an explanation for the general absence of collective fluctuations in the HHS low frequency vibrational region that we have detected experimentally. If we assume that the possible water-mediated interaction sites on the hydrophobic protein surface are by nature somewhat limited, then an excess amount of solvent in the hydration shell may drive the water molecules present in the layer to maximize their interactions with each other rather than with the protein. Recalling that the interaction of the solvent has been conjectured to be central to the eventual development of protein anharmonic fluctuations above the glass transition, we note that in our experiments we have observed that the types of surface interactions that HHS shares with the solvent include mostly localized side-chain torsions that do not change appreciably during the transition (Figure 1). Experimentally, we detect only a small rise in protein global mode peak intensities as the temperature is increased above the glass transition region indicating that the detected vibrational modes in the HHS spectra are restrained to harmonic oscillations.
Localized protein interactions and long-range communication in crambin
The origin of long-range communication in crambin?
Experimental detection of “more” localized intra-protein interactions and the formation of protein long-range coherence pathways in crambin
In this work we have explored the THz time scale fluctuations in crambin both from below and above the glass transition temperature. In line with previous investigations ,-–,,,,, we have deduced that the solvent fluctuations on a picosecond time scale strongly influence the protein fluctuations on an equivalent time scale. Through association with the solvent, we find that a sample with only the first hydration filled (LHS) has large-amplitude, anharmonic fluctuations as the glass transition temperature is approached. The LHS interacts with solvent water with an open, chain-like network, and the solvent-protein interactions in LHS promote collective backbone modes that extend throughout the entire protein. The HHS interactions with the solvent do not support anharmonic fluctuations and the progression through the glass transition is somewhat unremarkable. Furthermore, the class of water structures in the HHS hydration shell that are available for the protein to interact appear to be quite dissimilar. And perhaps as a consequence, the types of surface interactions that HHS shares with the solvent include mostly localized side-chain torsions that do not change appreciably during the transition. In light of these findings, it is possible that the pattern that we have observed experimentally simply reflects the hydrophobic nature of crambin; but it may also serve as a model for understanding sub-nanosecond protein-solvent coupled interactions in globular proteins in a broader sense.
So far, we have proposed that a general explanation for the differences in the crambin spectra in the low frequency THz region is the manner in which the solvent couples to the protein low frequency modes. The standard model  of the glass transition describes a particle moving across a rugged energy landscape, and below the transition temperature the particle is confined within a potential well. Near and above the transition temperature, the particle is able to overcome some of the lower barriers, resulting in what is referred to as “β- relaxation processes”. The β-relaxation process in proteins involves cooperative backbone fluctuations on a picosecond time scale. It has been conjectured that the fast conformational fluctuations connected with the β-process are a precursor for overcoming larger barriers associated with a principal α-relaxation (large-scale protein conformational change) that occurs on a much longer time scale . In the LHS spectra we find that the solvent coupling promotes large amplitude collective fluctuations in the protein when the transition temperature is reached. Indirect analysis of the water structure (Figure 6) in the LHS hydration shell has revealed an open water structure with a distinctive translational mode temperature dependency. It is through the dynamics of this less-ordered water structure that we surmise that the H-bonding network vibrations in the LHS support not only anharmonic fluctuations but also vibrational mode delocalization (vibrational modes that involve the entire protein) on a picosecond time scale. The HHS spectra reveal an entirely different story. The protein coupling with the solvent in HHS results in mostly localized, harmonic fluctuations in the ≤ 200 cm−1 spectral region. The basis for the localized fluctuations in HHS could be due to the overall rigidity of the H-bonding in the solvent network; or perhaps, a consequence of the protein being excluded from the aforementioned network and as an outcome unable to overcome barrier crossings. In actuality, the details pertaining to the interactions taking place within the extended solvent H-bonding network are beyond the scope of our current work on crambin and therefore, at this stage are mostly just speculation. The central issue from our analysis is that the nature of the protein-solvent coupling in HHS differs from LHS on the picosecond time scale. These distinctions appear to have significant ramifications for both the amplitude and characteristics of the low frequency protein modes detected in the THz experimental spectrum. The collective excitations that emerge after the glass transition in LHS may serve as a model for forming a better understanding about the types of motions that are generally triggered during the onset of the transition in hydrated globular proteins. Characterization of the THz time scale vibrational modes in the protein may also provide an opportunity to begin to elucidate the functional role of crambin.
Crambin was purchased from GenScript (Piscataway, NJ). Salt and other contaminations were removed from the sample prior to the experiment, by acetone precipitation and re-suspended in a buffer consisting of 10 mM NaH2PO4 and 0.01 mM ethylenediaminetetraacetic acid at pH 7.0. The concentration of the protein sample was determined by UV absorbance using a standard curve derived from a series of dilutions at 280 nm. The crambin samples used in the experiments were initially prepared by diluting the stock protein sample to a concentration of 1 mg/ml. 20 μL (~20 μg) of the diluted sample was subsequently placed on a high resistivity silicon window and excess water was removed by applying a low, steady flow of N2 gas over the sample droplet for approximately 10 minutes. The resulting protein film was subsequently rehydrated by equilibrating the partially dried sample in a vacuum sealed container with the vapor pressure of a saturated salt solution at 20°C for a minimum of 5 days . The low hydration crambin sample was hydrated with a saturated salt solution of NaCl while the fully hydrated crambin sample was hydrated with a saturated salt solution of K2SO4. The number of water molecules in the hydrated protein samples was estimated by thermal gravimetric analysis. Experimental measurements on hydrated, unoriented crambin film samples prepared from saturated salt solutions in this manner have revealed that samples equilibrated with a saturated salt solution of K2SO4 result in a hydration level of approximately 0.8 g/g. At this hydration level, the water molecules available in the hydration layer are sufficient for completing both the first and second hydration shell of the globular protein . The sample prepared in the presence of a saturated solution of NaCl result in hydration level of approximately 0.25 g/g and in this case the number of water molecules available is adequate for hydrating both polar and non-polar residue surface groups in the protein .
The prepared film sample was placed in a sealed transmission cell consisting of two high resistivity silicon substrates and a saturated salt solution was placed at the bottom of the cell to ensure that hydration was maintained throughout the experiment. Experiments with D2O as the solvent were prepared in a similar manner except that the crambin sample was dissolved in D2O rather than water. The D2O solution sample was initially allowed to equilibrate for two days at 4°C and then the D2O film samples were prepared and allowed to equilibrate at room temperature for another 5 days prior to experiment.
Molecular dynamics simulations
The molecular dynamics (MD) simulations were carried with the Gromacs package  version 4.5.3 using the all-atom OPS force field. A starting structure of the crambin configuration was initially downloaded from the protein databank (1EJG.pdb). For the low hydration sample the protein was initially hydrated with solvent molecules in a 3.8 Å shell surrounding the protein surface, which corresponds to 270 water molecules. The sample with higher hydration content consists of 854 water molecules and corresponds to a hydration shell that extends out to 8.0 Å from the protein surface. In the simulations, the SPC model of water was used. Energy minimization of the hydrated protein system was carried out by using a steepest descent method to a convergence tolerance of 0.001 kJ mol−1. The energy minimization was followed by a MD run with constraints for 200 ps in which an isotropic force constant of 100 kJ mol−1 nm−1 was used on the protein atoms. During the restrained dynamics simulation, the temperature and pressure of the system were kept constant by weak coupling to a modified velocity rescaled Berendsen temperature and pressure baths  and in all cases the protein and water molecules have been coupled to the temperature and pressure baths separately. The final output configuration from the MD simulation with constraints was used as the starting configuration for a 5 ns equilibration MD simulation run. Equilibration steps were performed with periodic boundary conditions. Configurations from the equilibration run were used as starting configurations for a series of 10 ns MD simulations. These final simulations were carried out with a 1 fs time step where the bonds between the hydrogen and the other heavier atoms were restrained to their equilibrium values with the linear constraints (LINCS) algorithm . Particle mesh Ewald (PME) method  was used to calculate the electrostatic interactions in the simulation and was used with a real-space cutoff of 1.0 nm, a fourth order B-spline interpolation and a Fourier spacing of 0.12 nm. In the MD simulations with heavy water, the water molecules were replaced with D2O.
where v refers to velocity and i denotes an atom or molecule in the simulation system. Fourier transform of the VACF is used to project out the underlying frequencies of the molecular processes associated with the correlated motions detected in the simulation.
which averages over hydrogen bond pairs, and has an either 0 or 1 (hb(τ) = [0,1]) for a particular hydrogen bond i at time t. In this analysis, a hydrogen bond is defined by using a geometrical criterion, where the center of mass distance is less than 3.5 Å, the r(O•••H) distance is smaller than 2.6 Å, and the ∠HO•••O angle is smaller than 30°. Other weak interactions (Van der Waals, electrostatic, etc.…) in the protein system are identified as contacts within an appropriate cut-off distance.
where i and j represent two separate residues and ∆r i and ∆r j are the displacement vectors of i and j where the brackets represent ensemble averages. In the cross correlation of the residue fluctuations if C ij = 1 then the fluctuations of i and j are completely correlated and if C ij = −1 then the fluctuations of i and j are completely anti-correlated and if C ij = 0 then the fluctuations of i and j are not correlated. In the graphical depiction of C ij only the magnitude of correlated fluctuations between residues with a value greater than 0.25 are considered.
THz spectroscopy experiments
To maintain the hydration level of the protein film during the experiment, the sample was placed in a sealed transmission cell consisting of two silicon windows. Reversibility of the temperature response of the protein sample, in terms of absorption features and intensity, was one criterion used to verify that the seal was maintained throughout the experiment. In the spectral measurements presented each scan consists of 16 averaged scans and the infrared data was collected with a spectral resolution of 4 cm−1 with an error of less than 2.0% between the individual scans used for averaging with the greatest error being found near the edges of the detection limits of the beam splitter. The 15–100 cm−1 THz spectra were collected with a 25 micron beam splitter while the data in the 100–250 cm−1 spectral region was collected with a 12 micron beam splitter. The temperature of the samples was varied using a SPECAC variable temperature cell. Using a combination of refrigerant and the control from the built-in temperature cell-block heaters, the temperature of the sample could be adjusted from −190°C to 30°C with stability of ± 0.1°C from the set temperature.
We would like to thank Dr. Bediha Beser for her helpful discussions on crambin during the early stages of this project.
- Hendrickson WA, Teeter MM: Structure of the hydrophobic protein crambin determined directly from the anomalous scattering of sulphur. Nature. 1981, 290: 107-113. 10.1038/290107a0.View ArticleGoogle Scholar
- Lobb L, Stec B, Kantrowitz EK, Yamano A, Stojanoff V, Markman O, Teeter MM: Expression, purification and characterization of recombinant crambin. Protein Eng. 1996, 9: 1233-1239. 10.1093/protein/9.12.1233.View ArticleGoogle Scholar
- Schmidt A, Teeter M, Weckert E, Lamzin VS: Crystal structure of small protein crambin at 0.48 Å resolution. Acta Crystallograph Sect F Struct Biol Cryst Commun. 2011, 67 (Pt 4): 424-428. 10.1107/S1744309110052607.View ArticleGoogle Scholar
- Ringe D, Petsko GA: The “glass transition” in protein dynamics: what it is, why it occurs, and how to exploit it. Biophys Chem. 2003, 105: 667-680. 10.1016/S0301-4622(03)00096-6.View ArticleGoogle Scholar
- Chen JC-H, Hanson BL, Fisher SZ, Langan P, Kovalevsky AY: Direct observation of hydrogen atom dynamics and interactions by ultrahigh resolution neutron protein crystallography. Proc Natl Acad Sci. 2012, 109: 15301-15306. 10.1073/pnas.1208341109.View ArticleGoogle Scholar
- Wand AJ: Dynamic activation of protein function: a view emerging from NMR spectroscopy. Nat Struct Mol Biol. 2001, 8: 926-931. 10.1038/nsb1101-926.View ArticleGoogle Scholar
- Jee J, Ahn H-C: Refinement of protein NMR structure under membrane-like environments with an implicit solvent model. Bull Korean Chem Soc. 2009, 30: 1139-1142. 10.5012/bkcs.2009.30.5.1139.View ArticleGoogle Scholar
- Johnson KA, Kim E, Teeter MM, Suh SW, Stec B: Crystal structure of α-hordothionin at 1.9 Å resolution. FEBS Lett. 2005, 579: 2301-2306. 10.1016/j.febslet.2004.12.100.View ArticleGoogle Scholar
- Doster W, Cusack S, Petry W: Dynamical transition of myoglobin revealed by inelastic neutron scattering. Nature. 1989, 337: 754-756. 10.1038/337754a0.View ArticleGoogle Scholar
- Berendsen HJ, Hayward S: Collective protein dynamics in relation to function. Curr Opin Struct Biol. 2000, 10: 165-169. 10.1016/S0959-440X(00)00061-0.View ArticleGoogle Scholar
- Tomita A, Sato T, Ichiyanagi K, Nozawa S, Ichikawa H, Chollet M, Kawai F, Park S-Y, Tsuduki T, Yamato T, Koshihara S-Y, Adachi S-I: Visualizing breathing motion of internal cavities in concert with ligand migration in myoglobin. Proc Natl Acad Sci U S A. 2009, 106: 2612-2616. 10.1073/pnas.0807774106.View ArticleGoogle Scholar
- Bakan A, Bahar I: The intrinsic dynamics of enzymes plays a dominant role in determining the structural changes induced upon inhibitor binding. Proc Natl Acad Sci. 2009, 106: 14349-14354. 10.1073/pnas.0904214106.View ArticleGoogle Scholar
- Teeter MM, Yamano A, Stec B, Mohanty U: On the nature of a glassy state of matter in a hydrated protein: relation to protein function. Proc Natl Acad Sci. 2001, 98: 11242-11247. 10.1073/pnas.201404398.View ArticleGoogle Scholar
- Paciaroni A, Cornicchi E, Marconi M, Orecchini A, Petrillo C, Haertlein M, Moulin M, Sacchetti F: Coupled relaxations at the protein–water interface in the picosecond time scale.J R Soc Interface 2009, rsif20090182.,
- Iben IET, Braunstein D, Doster W, Frauenfelder H, Hong MK, Johnson JB, Luck S, Ormos P, Schulte A, Steinbach PJ, Xie AH, Young RD: Glassy behavior of a protein. Phys Rev Lett. 1989, 62: 1916-1919. 10.1103/PhysRevLett.62.1916.View ArticleGoogle Scholar
- Jansson H, Bergman R, Swenson J: Role of solvent for the dynamics and the glass transition of proteins. J Phys Chem B. 2011, 115: 4099-4109. 10.1021/jp1089867.View ArticleGoogle Scholar
- Vitkup D, Ringe D, Petsko GA, Karplus M: Solvent mobility and the protein “glass” transition. Nat Struct Mol Biol. 2000, 7: 34-38. 10.1038/71231.View ArticleGoogle Scholar
- Young RD: Scaling law for the glass and ferry temperatures in the gaussian random energy model. J Chem Phys. 1993, 98: 2488-2489. 10.1063/1.464182.View ArticleGoogle Scholar
- Teeter MM, Case DA: Harmonic and quasiharmonic descriptions of crambin. J Phys Chem. 1990, 94: 8091-8097. 10.1021/j100384a021.View ArticleGoogle Scholar
- Bryngelson JD, Wolynes PG: Intermediates and barrier crossing in a random energy model (with applications to protein folding). J Phys Chem. 1989, 93: 6902-6915. 10.1021/j100356a007.View ArticleGoogle Scholar
- Bellissent-Funel M-C: Hydration in protein dynamics and function. J Mol Liq. 2000, 84: 39-52. 10.1016/S0167-7322(99)00109-9.View ArticleGoogle Scholar
- Fenimore PW, Frauenfelder H, McMahon BH, Parak FG: Slaving: solvent fluctuations dominate protein dynamics and functions. Proc Natl Acad Sci. 2002, 99: 16047-16051. 10.1073/pnas.212637899.View ArticleGoogle Scholar
- Roh JH, Novikov VN, Gregory RB, Curtis JE, Chowdhuri Z, Sokolov AP: Onsets of anharmonicity in protein dynamics. Phys Rev Lett. 2005, 95: 038101-10.1103/PhysRevLett.95.038101.View ArticleGoogle Scholar
- Goldanskii VI, Krupyanskii YF: Protein and protein-bound water dynamics studied by Rayleigh scattering of Mössbauer radiation (RSMR). Q Rev Biophys. 1989, 22: 39-92. 10.1017/S003358350000336X.View ArticleGoogle Scholar
- Zhang L, Wang L, Kao Y-T, Qiu W, Yang Y, Okobiah O, Zhong D: Mapping hydration dynamics around a protein surface. Proc Natl Acad Sci. 2007, 104: 18461-18466. 10.1073/pnas.0707647104.View ArticleGoogle Scholar
- Roh JH, Curtis JE, Azzam S, Novikov VN, Peral I, Chowdhuri Z, Gregory RB, Sokolov AP: Influence of hydration on the dynamics of lysozyme. Biophys J. 2006, 91: 2573-2588. 10.1529/biophysj.106.082214.View ArticleGoogle Scholar
- Ebbinghaus S, Kim SJ, Heyden M, Yu X, Heugen U, Gruebele M, Leitner DM, Havenith M: An extended dynamical hydration shell around proteins. Proc Natl Acad Sci. 2007, 104: 20749-20752. 10.1073/pnas.0709207104.View ArticleGoogle Scholar
- Bye JW, Meliga S, Ferachou D, Cinque G, Zeitler JA, Falconer RJ: Analysis of the hydration water around bovine serum albumin using terahertz coherent synchrotron radiation. J Phys Chem A. 2014, 118: 83-88. 10.1021/jp407410g.View ArticleGoogle Scholar
- Doster W: The protein-solvent glass transition. Biochim Biophys Acta BBA. 1804, 2010: 3-14.Google Scholar
- Heyden M, Sun J, Funkner S, Mathias G, Forbert H, Havenith M, Marx D: Dissecting the THz spectrum of liquid water from first principles via correlations in time and space. Proc Natl Acad Sci. 2010, 107: 12068-12073. 10.1073/pnas.0914885107.View ArticleGoogle Scholar
- Woods KN: Using THz time-scale infrared spectroscopy to examine the role of collective, thermal fluctuations in the formation of myoglobin allosteric communication pathways and ligand specificity. Soft Matter. 2014, 10: 4387-4402. 10.1039/c3sm53229a.View ArticleGoogle Scholar
- Woods KN: Solvent-induced backbone fluctuations and the collective librational dynamics of lysozyme studied by terahertz spectroscopy. Phys Rev E. 2010, 81: 031915-10.1103/PhysRevE.81.031915.View ArticleGoogle Scholar
- Woods KN: THz time scale structural rearrangements and binding modes in lysozyme-ligand interactions. J Biol Phys. 2014, 40: 121-137. 10.1007/s10867-014-9341-4.View ArticleGoogle Scholar
- Tarek M, Tobias DJ: Effects of solvent damping on side chain and backbone contributions to the protein boson peak. J Chem Phys. 2001, 115: 1607-1612. 10.1063/1.1380708.View ArticleGoogle Scholar
- Leyser H, Doster W, Diehl M: Far-infrared emission by boson peak vibrations in a globular protein. Phys Rev Lett. 1999, 82: 2987-2990. 10.1103/PhysRevLett.82.2987.View ArticleGoogle Scholar
- Paciaroni A, Bizzarri AR, Cannistraro S: Neutron scattering evidence of a boson peak in protein hydration water. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Top. 1999, 60: R2476-R2479.Google Scholar
- Tarek M, Tobias DJ: Single-particle and collective dynamics of protein hydration water: a molecular dynamics study. Phys Rev Lett. 2002, 89: 275501-10.1103/PhysRevLett.89.275501.View ArticleGoogle Scholar
- Shintani H, Tanaka H: Universal link between the boson peak and transverse phonons in glass. Nat Mater. 2008, 7: 870-877. 10.1038/nmat2293.View ArticleGoogle Scholar
- Joti Y, Nakagawa H, Kataoka M, Kitao A: Hydration effect on low-frequency protein dynamics observed in simulated neutron scattering spectra. Biophys J. 2008, 94: 4435-4443. 10.1529/biophysj.107.118042.View ArticleGoogle Scholar
- Born B, Kim SJ, Ebbinghaus S, Gruebele M, Havenith M: The terahertz dance of water with the proteins: the effect of protein flexibility on the dynamical hydration shell of ubiquitin. Faraday Discuss. 2009, 141: 161-10.1039/b804734k.View ArticleGoogle Scholar
- Zhong D, Pal SK, Zewail AH: Biological water: a critique. Chem Phys Lett. 2011, 503: 1-11. 10.1016/j.cplett.2010.12.077.View ArticleGoogle Scholar
- Cioni P, Strambini GB: Effect of heavy water on protein flexibility. Biophys J. 2002, 82: 3246-3253. 10.1016/S0006-3495(02)75666-X.View ArticleGoogle Scholar
- Ding T, Huber T, Middelberg APJ, Falconer RJ: Characterization of low-frequency modes in aqueous peptides using far-infrared spectroscopy and molecular dynamics simulation. J Phys Chem A. 2011, 115: 11559-11565. 10.1021/jp200553d.View ArticleGoogle Scholar
- He Y, Chen J-Y, Knab JR, Zheng W, Markelz AG: Evidence of protein collective motions on the picosecond timescale. Biophys J. 2011, 100: 1058-1065. 10.1016/j.bpj.2010.12.3731.View ArticleGoogle Scholar
- Kumar P, Wikfeldt KT, Schlesinger D, Pettersson LGM, Stanley HE: The Boson peak in supercooled water.Sci Rep 2013, 3.,
- Taschin A, Bartolini P, Eramo R, Righini R, Torre R: Evidence of two distinct local structures of water from ambient to supercooled conditions.Nat Commun 2013, 4.,
- Kim CU, Tate MW, Gruner SM: Protein dynamical transition at 110 K. Proc Natl Acad Sci. 2011, 108: 20897-20901. 10.1073/pnas.1110840108.View ArticleGoogle Scholar
- Fanetti S, Lapini A, Pagliai M, Citroni M, Di Donato M, Scandolo S, Righini R, Bini R: Structure and dynamics of low-density and high-density liquid water at high pressure. J Phys Chem Lett. 2014, 5: 235-240. 10.1021/jz402302z.View ArticleGoogle Scholar
- Gaiduk VI, Vij JK: The concept of two stochastic processes in liquid water and analytical theory of the complex permittivity in the wavenumber range 0–1000 cm − 1. Phys Chem Chem Phys. 2001, 3: 5173-5181. 10.1039/b106510f.View ArticleGoogle Scholar
- Brubach J-B, Mermet A, Filabozzi A, Gerschel A, Roy P: Signatures of the hydrogen bonding in the infrared bands of water. J Chem Phys. 2005, 122: 184509-10.1063/1.1894929.View ArticleGoogle Scholar
- Stenger J, Madsen D, Dreyer J, Nibbering ETJ, Hamm P, Elsaesser T: Coherent response of hydrogen bonds in liquids probed by ultrafast vibrational spectroscopy. J Phys Chem A. 2001, 105: 2929-2932. 10.1021/jp003153h.View ArticleGoogle Scholar
- Tournier AL, Xu J, Smith JC: Translational hydration water dynamics drives the protein glass transition. Biophys J. 2003, 85: 1871-1875. 10.1016/S0006-3495(03)74614-1.View ArticleGoogle Scholar
- Markelz AG, Knab JR, Chen JY, He Y: Protein dynamical transition in terahertz dielectric response. Chem Phys Lett. 2007, 442: 413-417. 10.1016/j.cplett.2007.05.080.View ArticleGoogle Scholar
- Klug DD, Zgierski MZ, Tse JS, Liu Z, Kincaid JR, Czarnecki K, Hemley RJ: Doming modes and dynamics of model heme compounds. Proc Natl Acad Sci. 2002, 99: 12526-12530. 10.1073/pnas.152464699.View ArticleGoogle Scholar
- Ding T, Middelberg APJ, Huber T, Falconer RJ: Far-infrared spectroscopy analysis of linear and cyclic peptides, and lysozyme. Vib Spectrosc. 2012, 61: 144-150. 10.1016/j.vibspec.2012.02.020.View ArticleGoogle Scholar
- Greve TM, Andersen KB, Nielsen OF, Engdahl A: FTIR imaging and ATR-FT-Far-IR synchrotron spectroscopy of pig ear skin. J Spectrosc. 2010, 24: 105-111. 10.1155/2010/716473.View ArticleGoogle Scholar
- Mizuguchi M, Nara M, Ke Y, Kawano K, Hiraoki T, Nitta K: Fourier-transform infrared spectroscopic studies on the coordination of the side-chain COO- groups to Ca2+ in equine lysozyme. Eur J Biochem FEBS. 1997, 250: 72-76. 10.1111/j.1432-1033.1997.00072.x.View ArticleGoogle Scholar
- Giraud G, Wynne K: Time-resolved optical Kerr-effect spectroscopy of Low-frequency dynamics in Di-l-alanine, poly-l-alanine, and lysozyme in solution. J Am Chem Soc. 2002, 124: 12110-12111. 10.1021/ja027801h.View ArticleGoogle Scholar
- Bermejo FJ, Alvarez M, Bennington SM, Vallauri R: Absence of anomalous dispersion features in the inelastic neutron scattering spectra of water at both sides of the melting transition. Phys Rev E. 1995, 51: 2250-2262. 10.1103/PhysRevE.51.2250.View ArticleGoogle Scholar
- Tych KM, Wood CD, Burnett AD, Pearson AR, Davies AG, Linfield EH, Cunningham JE: Probing temperature- and solvent-dependent protein dynamics using terahertz time-domain spectroscopy. J Appl Crystallogr. 2014, 47: 146-153. 10.1107/S1600576713029506.View ArticleGoogle Scholar
- Ngai KL, Capaccioli S, Shinyashiki N: The protein “glass” transition and the role of the solvent. J Phys Chem B. 2008, 112: 3826-3832. 10.1021/jp710462e.View ArticleGoogle Scholar
- Poole P, Finney J: Solid-phase protein hydration studies. Methods Enzym. 1986, 127: 284-293. 10.1016/0076-6879(86)27023-8.View ArticleGoogle Scholar
- Sartor G, Hallbrucker A, Mayer E: Characterizing the secondary hydration shell on hydrated myoglobin, hemoglobin, and lysozyme powders by its vitrification behavior on cooling and its calorimetric glass liquid transition and crystallization behavior on reheating. Biophys J. 1995, 69: 2679-2694. 10.1016/S0006-3495(95)80139-6.View ArticleGoogle Scholar
- Lindahl E, Hess B, van der Spoel D: GROMACS 3.0: a package for molecular simulation and trajectory analysis. Mol Model Annu. 2001, 7: 306-317.Google Scholar
- Berendsen JC, Postma JPM, van Gunsteren WF, DiNola A, Haak JR: Molecular dynamics with coupling to an external bath. J Chem Phys. 1984, 81: 3684-3690. 10.1063/1.448118.View ArticleGoogle Scholar
- Hess HBB, Berendsen JC, Fraaije JGEM: LINCS: a linear constraint solver for molecular simulations. J Comput Chem. 1997, 18: 1463-1472. 10.1002/(SICI)1096-987X(199709)18:12<1463::AID-JCC4>3.0.CO;2-H.View ArticleGoogle Scholar
- Essmann U, Perera L, Berkowitz ML, Darden T, Lee H, Pedersen LG: A smooth particle mesh Ewald method. J Chem Phys. 1995, 103: 8577-8593. 10.1063/1.470117.View ArticleGoogle Scholar
- Pronk S, Páll S, Schulz R, Larsson P, Bjelkmar P, Apostolov R, Shirts MR, Smith JC, Kasson PM, Van Der SD, Hess B, Lindahl E: GROMACS 4.5: a high-throughput and highly parallel open source molecular simulation toolkit. Bioinformatics. 2013, 29: 845-854. 10.1093/bioinformatics/btt055.View ArticleGoogle Scholar
- Starr FW, Nielsen JK, Stanley HE: Hydrogen-bond dynamics for the extended simple point-charge model of water. Phys Rev E. 2000, 62: 579-587. 10.1103/PhysRevE.62.579.View ArticleGoogle Scholar
- Ackermann T, Brooks CL, Karplus M, Pettitt BM: Proteins: a theoretical perspective of dynamics, structure and thermodynamics, volume LXXI, in: advances in chemical physics, John Wiley & Sons, New York 1988. Berichte Bunsenges Für Phys Chem. 1990, 94: 96-96. 10.1002/bbpc.19900940129.View ArticleGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.