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PubMed1988

Refinement of the solution structure of the ribonucleotide 5'r(GCAUGC)2: combined use of nuclear magnetic resonance and restrained molecular dynamics.

The solution structure of the self-complementary hexamer 5'r(GCAUGC)2 is investigated by means of nuclear magnetic resonance spectroscopy and restrained molecular dynamics. The proton resonances are assigned in a sequential manner, and a set of 110 approximate interproton distance restraints are derived from the two-dimensional nuclear Overhauser enhancement spectra. These distances are used as the basis of a structure refinement by restrained molecular dynamics in which the experimental restraints are incorporated into the total energy function of the system in the form of effective potentials. Eight restrained molecular dynamics simulations are carried out, four starting from a structure with regular A-type geometry and four from one with regular B-type geometry. The atomic root mean square (rms) difference between the initial structures is 3.2 A. In the case of all eight simulations, convergence is achieved both globally and locally to a set of very similar A-type structures with an average atomic rms difference between them of 0.8 +/- 0.2 A. Further, the atomic rms differences between the restrained dynamics structures obtained by starting out from the same initial structures but with different random number seeds for the assignment of the initial velocities are the same as those between the restrained dynamics structures starting out from the two different initial structures. These results suggest that the restrained dynamics structures represent good approximations of the solution structure. The converged structures exhibit clear sequence-dependent variation in some of the helical parameters, in particular helix twist, roll, slide, and propellor twist.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1988

Theoretical studies of the structure and molecular dynamics of a peptide crystal.

Energy minimizations and molecular dynamics simulations have been performed on the cyclic peptide cyclo-(Ala-Pro-D-Phe)2 in both the isolated and crystal states. The results of these calculations have been analyzed, both to investigate our ability to reproduce experimental data (structure and vibrational and NMR spectra) and to investigate the effects of environment on the energy, structure, and dynamics of peptides. Comparison of the minimized and time-averaged crystal systems with the experimental peptide structure shows that the calculations have closely reproduced the experimental structure. Molecular dynamics of the isolated molecule has led to a new conformation, which is approximately equal to 8.5 kcal/mol more stable than the conformation that exists in the crystal, the latter conformation being stabilized by intermolecular (packing) forces. This illustrates the considerable effect that environment can have on the conformation of peptides. The crystal environment has also been shown to significantly reduce the dynamic conformational fluctuations seen for the isolated molecule. The behavior of the peptide during the isolated simulation also supports the experimental NMR observation of a symmetric structure that differs from the asymmetric, instantaneous structures which characterize the molecule during the dynamics. Calculations of vibrational frequencies of the peptide in the crystal and isolated states show the expected shifts in bond-stretching frequencies due to intermolecular interactions. Finally, we have calculated NMR coupling constants from the dynamics simulation of the isolated peptide and have compared these with the experimental values. This has led to a possible reinterpretation of the experimental data.

Crystallization↗
PubMed1990

Determination of the conformation of d(GGAAATTTCC)2 in solution by use of 1H NMR and restrained molecular dynamics.

The conformation of the putative bent DNA d(GGAAATTTCC)2 in solution was studied by use of 1H NMR and restrained molecular dynamics. Most of the resonances were assigned sequentially. A total of 182 interproton distance restraints were determined from two-dimensional nuclear Overhauser effect spectra with short mixing times. Torsion angle restraints for each sugar moiety were determined by qualitative analysis of a two-dimensional correlated spectrum. Restrained molecular dynamics was carried out with the interproton distances and torsion angles incorporated into the total energy function of the system in the form of effective potential terms. As initial conformations for restrained molecular dynamics, classical A-DNA and B-DNA were adopted. The root mean square deviation (rmsd) between these two conformations is 5.5 A. The conformations obtained by use of restrained molecular dynamics are very similar to each other, the rmsd being 0.8 A. On the other hand, the conformations obtained by use of molecular dynamics without experimental restraints or restrained energy minimization depended heavily on the initial conformations, and convergence to a similar conformation was not attained. The conformation obtained by use of restrained molecular dynamics exhibits a few remarkable features. The second G residue takes on the BII conformation [Fratini, A. V., Kopka, M. L., Drew, H. R., & Dickerson, R. E. (1982) J. Biol. Chem. 257, 14686-14707] rather than the standard BI conformation. There is discontinuity of the sugar puckering between the eighth T and ninth C. The minor groove of the oligo(dA) tract is rather compressed. As a result, d(GGAAATTTCC)2 is bent.

Magnetic Resonance Spectroscopy↗
PubMed2002

Ligand-induced conformational and structural dynamics changes in Escherichia coli cyclic AMP receptor protein.

Cyclic AMP receptor protein (CRP) regulates the expression of a large number of genes in E. coli. It is activated by cAMP binding, which leads to some yet undefined conformational changes. These changes do not involve significant redistribution of secondary structures. A potential mechanism of activation is a ligand-induced change in structural dynamics. Hence, the cAMP-mediated conformational and structural dynamics changes in the wild-type CRP were investigated using hydrogen-deuterium exchange and Fourier transform infrared spectroscopy. Upon cAMP binding, the two functional domains within the wild-type CRP undergo conformational and structural dynamics changes in two opposite directions. While the smaller DNA-binding domain becomes more flexible, the larger cAMP-binding domain shifts to a less dynamic conformation, evidenced by a faster and a slower amide H-D exchange, respectively. To a lesser extent, binding of cGMP, a nonfunctional analogue of cAMP, also stabilizes the cAMP-binding domain, but it fails to mimic the relaxation effect of cAMP on the DNA-binding domain. Despite changes in the conformation and structural dynamics, cAMP binding does not alter significantly the secondary structural composition of the wild-type CRP. The apparent difference between functional and nonfunctional analogues of cAMP is the ability of cAMP to effect an increase in the dynamic motions of the DNA binding domain.

Binding Sites↗
PubMed2003

DNA dynamics in RecA-DNA filaments: ATP hydrolysis-related flexibility in DNA.

RecA-catalyzed DNA recombination is initiated by a mandatory, high-energy form of DNA in RecA-nucleoprotein filaments, where bases are highly unstacked and the backbone is highly unwound. Interestingly, only the energetics consequent to adenosine triphosphate (ATP) binding, rather than its hydrolysis, seems sufficient to mediate such a high-energy structural hallmark of a recombination filament. The structural consequence of ATP hydrolysis on the DNA part of the filament thus remains largely unknown. We report time-resolved fluorescence dynamics of bases in RecA-DNA complexes and demonstrate that DNA bases in the same exhibit novel, motional dynamics with a rotational correlation time of 7-10 ns, specifically in the presence of ATP hydrolysis. When the ongoing ATP hydrolysis of RecA-DNA filament is "poisoned" by a nonhydrolyzable form of ATP (ATPgammaS), the motional dynamics cease and reveal a global motion with a rotational correlation time of >20 ns. Such ATP hydrolysis-induced flexibility ensues in single-stranded as well as double-stranded bases of RecA-DNA filaments. These results suggest that the role of ATP hydrolysis is to induce a high level of backbone flexibility in RecA-DNA filament, a dynamic property that is likely to be important for efficient strand exchanges in ATP hydrolysis specific RecA reactions. It is the absence of these motions that may cause high rigidity in RecA-DNA filaments in ATPgammaS. Dynamic light scattering measurement comparisons of RecA-ss-DNA filaments formed in ATPgammaS vs that of ATP confirmed such an interpretation, where the former showed a complex of larger (30 nm) hydrodynamic radius than that of latter (12-15 nm). Taken together, these results reveal a more dynamic state of DNA in RecA-DNA filament that is hydrolyzing ATP, which encourage us to model the role of ATP hydrolysis in RecA-mediated DNA transactions.

Adenosine Triphosphate↗
PubMed2004

Hydrophobic core fluidity of homologous protein domains: relation of side-chain dynamics to core composition and packing.

The side-chain dynamics of methyl groups in two structurally related proteins from the fibronectin type III (fnIII) superfamily, the third fnIII domain from human tenascin (TNfn3) and the tenth fnIII domain from human fibronectin (FNfn10), have been studied by NMR spectroscopy. Side-chain order parameters reveal that the hydrophobic cores of the two proteins have substantially different mobilities. The core of TNfn3 is very dynamic, with exceptionally low order parameters for the most deeply buried residues, while that of FNfn10 is more like those of other proteins which have been studied with this technique, having a relatively rigid core with uniformly distributed dynamics. The unusually dynamic core of TNfn3 appears to be related to its amino acid composition, which makes it more fluid-like. A further explanation for the mobility of the TNfn3 core may be found in the negative correlation between the order parameter and excess packing volume, which shows that the core of TNfn3 is less densely packed and consequently has lower methyl order parameters for its buried residues. Rotameric transitions, presumably facilitated by the lower packing density, appear to make an important contribution to lowering the order parameters, and have been probed by measuring three-bond scalar couplings. Overall, although backbone dynamics is generally similar for proteins with the same topology on a fast time scale (picoseconds to nanoseconds), this study shows that a single fold can accommodate a wide variation in the dynamic properties of its core.

Amino Acid Sequence↗
PubMed2006

Structural dynamics and topology of phospholamban in oriented lipid bilayers using multidimensional solid-state NMR.

Phospholamban (PLN), a single-pass membrane protein, regulates heart muscle contraction and relaxation by reversible inhibition of the sarco(endo)plasmic reticulum Ca-ATPase (SERCA). Studies in detergent micelles and oriented lipid bilayers have shown that in its monomeric form PLN adopts a dynamic L shape (bent or T state) that is in conformational equilibrium with a more dynamic R state. In this paper, we use solid-state NMR on both uniformly and selectively labeled PLN to refine our initial studies, describing the topology and dynamics of PLN in oriented lipid bilayers. Two-dimensional PISEMA (polarization inversion spin exchange at the magic angle) experiments carried out in DOPC/DOPE mixed lipid bilayers reveal a tilt angle of the transmembrane domain with respect to the static magnetic field, of 21 +/- 2 degrees and, at the same time, map the rotation angle of the transmembrane domain with respect to the bilayer. PISEMA spectra obtained with selectively labeled samples show that the cytoplasmic domain of PLN is helical and makes an angle of 93 +/- 6 degrees with respect to the bilayer normal. In addition, using samples tilted by 90 degrees , we find that the transmembrane domain of PLN undergoes fast long-axial rotational diffusion about the bilayer normal with the cytoplasmic domain undergoing this motion and other complex dynamics, scaling the values of chemical shift anisotropy. While this dynamic was anticipated by previous solution NMR relaxation studies in micelles, these measurements in the anisotropic lipid environment reveal new dynamic and conformational features encoded in the free protein that might be crucial for SERCA recognition and subsequent inhibition.

Calcium-Binding Proteins↗
PubMed2001

Ultrafast dynamics in aqueous polyacrylamide solutions.

We have investigated the ultrafast dynamics of aqueous polyacrylamide ([-CH(2)CH(CONH(2))-](n), or PAAm) solutions using femtosecond optical heterodyne-detected Raman-induced Kerr effect spectroscopy (OHD-RIKES). The observed aqueous PAAm dynamics are nearly identical for both M(w) = 1500 and 10 000. Aqueous propionamide (CH(3)CH(2)CONH(2), or PrAm) solutions were also studied, because PrAm is an exact model for the PAAm constitutional repeat unit (CRU). The longest time scale dynamics observed for both aqueous PAAm and PrAm solutions occur in the 4-10 ps range. Over the range of concentrations from 0 to 40 wt %, the picosecond reorientation time constants for the aqueous PAAm and PrAm solutions scale linearly with the solution concentration, despite the fact that the solution shear viscosities vary exponentially from 1 to 264 cP. For a given value of solution concentration in weight percent, constant ratios of measured reorientation time constants for PAAm to PrAm are obtained. This ratio of PAAm to PrAm reorientation time constants is equal to the ratio of the volume for the PAAm constitutional repeat unit (-CH(2)CHCONH(2)-) to the molecular volume of PrAm. For these reasons, we assign the polymer reorientation dynamics to motions of the entire constitutional repeat unit, not only side group motions. Simple molecular dynamics simulations of H[-CH(2)CH(CONH(2))-](7)H in a periodic box with 180 water molecules support this assignment. Amide-amide and amide-water hydrogen-bonding interactions lead to strongly oscillatory femtosecond dynamics in the Kerr transients, peaking at 80, 410, and 750 fs.

Journal Article↗
PubMed2004

Dynamics of hemoglobin in human erythrocytes and in solution: influence of viscosity studied by ultrafast vibrational echo experiments.

Ultrafast spectrally resolved stimulated vibrational echo experiments are used to measure the vibrational dephasing of the CO stretching mode of hemoglobin-CO (HbCO) inside living human erythrocytes (red blood cells), in liquid solutions, and in a glassy matrix. A method is presented to overcome the adverse impact on the vibrational echo signal from the strong light scattering caused by the cells. The results from the cytoplasmic HbCO are compared to experiments on aqueous HbCO samples prepared in different buffers, solutions containing low and high concentrations of glycerol, and in a solid trehalose matrix. Measurements are also presented that provide an accurate determination of the viscosity at the very high Hb concentration that is found inside the cells. It is demonstrated that the dynamics of the protein, as sensed by the CO ligand, are the same inside the erythrocytes and in aqueous solution and are independent of the viscosity. In solutions that are predominantly glycerol, the dynamics are modified somewhat but are still independent of viscosity. The experiments in trehalose give the dynamics at infinite viscosity and are used to separate the viscosity-dependent dynamics from the viscosity-independent dynamics. Although the HbCO dynamics are the same in the red blood cell and in the equivalent aqueous solutions, differences in the absorption spectra show that the distribution of a protein's equilibrium substates is sensitive to small pH differences.

Erythrocytes↗
PubMed2005

Changes in calmodulin main-chain dynamics upon ligand binding revealed by cross-correlated NMR relaxation measurements.

The fast dynamics of protein backbones are often investigated by nuclear magnetic relaxation experiments that report on the degree of spatial restriction of the amide bond vector. By comparing calmodulin in the peptide-bound and peptide-free states with these classical methods, we observe little difference in the dynamics of the polypeptide main chain (average order parameter decrease of 0.01 unit upon binding). However, when using NMR methods that monitor the mobility of the CO-Calpha bond vector, we reveal a significant reduction of dynamics of the protein main chain (average order parameter decrease of 0.048 units). Previous investigations have suggested that the side-chain dynamics is reduced by an average of 0.07 order parameter units upon ligand binding (Lee, A. L.; Kinnear, S. A.; Wand, A. J. Nat. Struct. Biol. 2000, 7, 72-77). The current findings suggest that the change of the CO-Calpha bond vector dynamics is intermediate between the changes in NH and side-chain dynamics and report a previously undetected loss of main-chain entropy. Weak site-to-site correlations between the different motional indicators are also observed.

Binding Sites↗
PubMed2003

Application of the lambda-dynamics method to evaluate the relative binding free energies of inhibitors to HCV protease.

The lambda-dynamics method was used to calculate the relative binding free energies of inhibitors to the hepatitis C virus (HCV) protease. A total of seven HCV protease p-side product inhibitors were used in this study. The inhibitors are 6-mer peptides spanning P6-P1 (Ac-Asp-d-Glu-Leu-Ile-Cha-P1-CO(2)H). For this protein, S1 is a major hydrophobic pocket for binding. Binding of various residues to this pocket was investigated through free energy simulations and experimental inhibition constants. Several 300 ps lambda-dynamics simulations in explicit solvent were performed. The relative binding free energy was estimated from these simulations. From a single simulation, the inhibitors can be correctly classified into highly potent and weakly potent groups. The multiple simulations give an accurate rank ordering of inhibitor potency; computed and experimental binding free energies agree with 0.6 kcal/mol for five of the seven inhibitors. In addition, free energy perturbation (FEP) calculations were carried out to validate the results from lambda-dynamics. A total of 6 ligand pairs were compared. For each pair, 5-11 windows were used to map one ligand to the other. The cumulative simulation time was over 2 ns for each ligand pair. For four of the six ligand pairs, the lambda-dynamics free energy difference fits better than the FEP difference to the experimental value. The fact that the lambda-dynamics method achieved similar results in only a fraction of the total simulation time for FEP further demonstrates the robustness of the lambda-dynamics method.

Endopeptidases↗
PubMed2000

Developing a dynamic pharmacophore model for HIV-1 integrase.

We present the first receptor-based pharmacophore model for HIV-1 integrase. The development of "dynamic" pharmacophore models is a new method that accounts for the inherent flexibility of the active site and aims to reduce the entropic penalties associated with binding a ligand. Furthermore, this new drug discovery method overcomes the limitation of an incomplete crystal structure of the target protein. A molecular dynamics (MD) simulation describes the flexibility of the uncomplexed protein. Many conformational models of the protein are saved from the MD simulations and used in a series of multi-unit search for interacting conformers (MUSIC) simulations. MUSIC is a multiple-copy minimization method, available in the BOSS program; it is used to determine binding regions for probe molecules containing functional groups that complement the active site. All protein conformations from the MD are overlaid, and conserved binding regions for the probe molecules are identified. Those conserved binding regions define the dynamic pharmacophore model. Here, the dynamic model is compared to known inhibitors of the integrase as well as a three-point, ligand-based pharmacophore model from the literature. Also, a "static" pharmacophore model was determined in the standard fashion, using a single crystal structure. Inhibitors thought to bind in the active site of HIV-1 integrase fit the dynamic model but not the static model. Finally, we have identified a set of compounds from the Available Chemicals Directory that fit the dynamic pharmacophore model, and experimental testing of the compounds has confirmed several new inhibitors.

Computer Simulation↗
PubMed2005

Dynamics of water trapped between hydrophobic solutes.

We describe the model dynamical behavior of the solvent between two nanoscopic hydrophobic solutes. The dynamics of the vicinal water in various sized traps is found to be significantly different from bulk behavior. We consider the dynamics at normal temperature and pressure at three intersolute distances corresponding to the three solvent separated minima in the free energy profile between the solutes with attractions. These three states correspond to one, two, and three intervening layers of water molecules. Results are obtained from a molecular dynamics simulation at constant temperature and pressure (NPT) ensemble. Translational diffusion of water molecules trapped between the two solutes has been analyzed from the velocity correlation function as well as from the mean square displacement of the water molecules. The rotational behavior has been analyzed through the reorientational dynamics of the dipole moment vector of the water molecule by calculating both first and second rank dipole-dipole correlation functions. Both the translational and reorientational mobilities of water are found to be much slower at the smaller separation and increases as the separation between solutes becomes larger. The occupation time distribution functions calculated from the trajectories also show that the relaxation is much slower for the smallest intersolute separation as compared to other wider separations. The sublinear trend in mean square displacement and the stretched exponential decay of the relaxation of dipolar correlation and occupation distribution function indicate that the dynamical behavior of water in the confined region between two large hydrophobic solutes departs from usual Brownian behavior. This behavior is reminiscent of the behavior of water in the vicinity of protein surface clefts or trapped between two domains of a protein.

Hydrophobic and Hydrophilic Interactions↗
PubMed2005

Tests of an approximate scaling principle for dynamics of classical fluids.

We used molecular dynamics computer simulations to test an approximate scaling principle that conjectures that two equilibrium atomic liquids have very similar dynamical properties if they have the same density and similar static pair correlation functions when the length scales of the two liquids are adjusted appropriately, even if they have different interatomic potentials and different temperatures. The simulations were performed on two types of model atomic liquids at various temperatures at the same density. In the first type, the interatomic potential is the Lennard-Jones potential (LJ). In the second type, the interatomic potential is the repulsive part of the Lennard-Jones potential (RLJ). We identified pairs of systems that have very similar pair correlation functions despite the fact that they had different potentials. Each pair consisted of an LJ liquid at a specific temperature and a corresponding RLJ liquid at a lower temperature. We compared various time correlation functions and transport coefficients of the two systems in each pair. Many dynamical properties are very similar in each pair, in accordance with the approximate scaling principle, whereas others are significantly different. The results indicate that certain dynamical properties are very insensitive to large changes in the interatomic potential that leave the pair correlation function largely unchanged, whereas other dynamical properties are much more sensitive to such changes in the potential. The transport coefficients for diffusion and viscosity are among the dynamical properties that are insensitive to such changes in the potential, and this may be part of the reason transport properties of many fluids have been calculated or rationalized in terms of a simple hard sphere model of liquids.

Journal Article↗
PubMed2005

Solvation dynamics of DCM in a DPPC vesicle entrapped in a sodium silicate derived sol-gel matrix.

Solvation dynamics of 4-(dicyanomethylene)-2-methyl-6(p-dimethylaminostyryl) 4H-pyran (DCM) has been studied in a dipalmitoyl-phosphatidylcholine (DPPC) vesicle entrapped in a sodium silicate derived sol-gel glass. Solvation dynamics in DPPC in a sol-gel glass is described by two components of 350 +/- 50 ps (50%) and 2300 +/- 200 ps (50%) with a total dynamic Stokes shift of 1300 cm(-1). The fast component (350 ps) is similar to the fast component in a DPPC vesicle in bulk water (320 +/- 50 ps). This component may be ascribed to the dynamics of the water molecules inside the water pool of the vesicle. However, the slow component (2300 +/- 200 ps) is about 2.5 times slower compared to the slow component of solvation dynamics of DCM in a DPPC vesicle in bulk solvent (900 +/- 100 ps). The anisotropy decay of DCM in a DPPC vesicle both in sol-gel glass and in bulk water exhibits a very fast initial decay with a large residual anisotropy, which does not decay in approximately 10 ns. The time scale of anisotropy decay is very different from that of solvation dynamics.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2005

Structural fluctuation and dynamics of ribose puckering in aqueous solution from first principles.

Using the method of ab initio molecular dynamics, we examine the structural fluctuation and the low-frequency dynamics of beta-ribofuranose puckering in aqueous solution. Our analysis suggests that the distance between the anomeric and hydroxymethyl oxygens is a simple relevant geometrical parameter that dynamically correlates with the phase angle in the north region. The time-frequency analysis using the Hilbert-Huang transform also confirms the correlation, and most of the instantaneous frequencies for the phase angle and the above distance are found to be concentrated on the region below about 100 cm(-1). Our analysis of ab initio molecular dynamics trajectories suggests that the molecular origin of the hydration effects on the low-frequency dynamics of beta-ribofuranose puckering is closely related to this correlation and thus primarily attributed to the relatively local interactions among the anomeric and hydroxymethyl oxygens and the surrounding water molecules near them. Additionally, we discuss the difference in the low-frequency dynamics of beta-ribofuranose puckering between two hydroxymethyl rotamers.

Computer Simulation↗
PubMed2005

Molecular view of water dynamics near model peptides.

Incoherent quasi-elastic neutron scattering (QENS) has been used to measure the dynamics of water molecules in solutions of a model protein backbone, N-acetyl-glycine-methylamide (NAGMA), as a function of concentration, for comparison with results for water dynamics in aqueous solutions of the N-acetyl-leucine-methylamide (NALMA) hydrophobic peptide at comparable concentrations. From the analysis of the elastic incoherent structure factor, we find significant fractions of elastic intensity at high and low concentrations for both solutes, which corresponds to a greater population of protons with rotational time scales outside the experimental resolution (>13 ps). The higher-concentration solutions show a component of the elastic fraction that we propose is due to water motions that are strongly coupled to the solute motions, while for low-concentration solutions an additional component is activated due to dynamic coupling between inner and outer hydration layers. An important difference between the solute types at the highest concentration studied is found from stretched exponential fits to their experimental intermediate scattering functions, showing more pronounced anomalous diffusion signatures for NALMA, including a smaller stretched exponent beta and a longer structural relaxation time tau than those found for NAGMA. The more normal water diffusion exhibited near the hydrophilic NAGMA provides experimental support for an explanation of the origin of the anomalous diffusion behavior of NALMA as arising from frustrated interactions between water molecules when a chemical interface is formed upon addition of a hydrophobic side chain, inducing spatial heterogeneity in the hydration dynamics in the two types of regions of the NALMA peptide. We place our QENS measurements on model biological solutes in the context of other spectroscopic techniques and provide both confirming as well as complementary dynamic information that attempts to give a unifying molecular view of hydration dynamics signatures near peptides and proteins.

Diffusion↗
PubMed2005

Structure and dynamics of the solvation of bovine pancreatic trypsin inhibitor in explicit water: a comparative study of the effects of solvent and protein polarizability.

To isolate the effects of the inclusion of polarizability in the force field model on the structure and dynamics of the solvating water in differing electrostatic environments of proteins, we present the results of molecular dynamics simulations of the bovine pancreatic trypsin inhibitor (BPTI) in water with force fields that explicitly include polarization for both the protein and the water. We use three model potentials for water and two model potentials for the protein. Two of the water models and one of the protein models are polarizable. A total of six systems were simulated representing all combinations of these polarizable and nonpolarizable protein and water force fields. We find that all six systems behave in a similar manner in regions of the protein that are weakly electrostatic (either hydrophobic or weakly hydrophilic). However, in the vicinity of regions of the protein with relatively strong electrostatic fields (near positively or negatively charged residues), we observe that the water structure and dynamics are dependent on both the model of the protein and the model of the water. We find that a large part of the dynamical dependence can be described by small changes in the local environments of each region that limit the local density of non-hydrogen-bonded waters, precisely the water molecules that facilitate the dynamical relaxation of the water-water hydrogen bonds. We introduce a simple method for rescaling for this effect. When this is done, we are able to effectively isolate the influence of polarizability on the dynamics. We find that the solvating water's relaxation is most affected when both the protein and the water models are polarizable. However, when only one model (or neither) is polarizable, the relaxation is similar regardless of the models used.

Animals↗