Dynamics of internal water in fatty acid binding protein: Computer simulations and comparison with experiments

Likić, Vladimir A; Prendergast, Franklyn G.

doi:10.1002/1097-0134(20010401)43:1<65::aid-prot1018>3.0.co;2-f

Cited by 34 publications

(31 citation statements)

References 31 publications

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“…Prendergast's group21, 36 has extensively studied a conserved, internal solvent site in fatty‐acid binding proteins using NMR, molecular dynamics simulations, and analysis of crystal structure data. In our study, this site corresponded to the top peak in the water distribution map (62σ), and the site had 100% conservation [Table II, Fig.…”

Section: Resultsmentioning

confidence: 99%

Exploring structurally conserved solvent sites in protein families

2006

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Protein-bound water molecules are important components of protein structure, and therefore, protein function and energetics. Although structural conservation of solvent has been studied in a few protein families, a lack of suitable computational tools has hindered more comprehensive analyses. Herein we present a semiautomated computational approach for identifying solvent sites that are conserved among proteins sharing a common three-dimensional structure. This method is tested on six protein families: (1) monodomain cytochrome c, (2) fatty-acid binding protein, (3) lactate/malate dehydrogenase, (4) parvalbumin, (5) phospholipase A2, and (6) serine protease. For each family, the method successfully identified previously known conserved solvent sites. Moreover, the method discovered 22 novel conserved solvent sites, some of which have higher degrees of conservation than the previously known sites. All six families studied had solvent sites with more than 90% conservation and these sites were invariably located in regions of the protein with very high sequence conservation. These results suggest that highly conserved solvent sites, by virtue of their proximity to conserved residues, should be considered as one of the defining three-dimensional structural characteristics of protein families and folds.

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Section: Resultsmentioning

confidence: 99%

Exploring structurally conserved solvent sites in protein families

2006

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“…The authors of [32] state that "When repeated from slightly different but equally plausible initial conditions, MD simulations of protein equilibrium dynamics predict different values for the same dynamic property of interest" [33][34][35]. The same authors [32] state that the variations occur because of insufficient sampling of protein's conformational space, an effect known as the "sampling problem" [34][35][36][37][38]. Most pico-to-nanosecond simulations of proteins and nucleic acids in water are considered to be not well equilibrated in some way, and are thought to contain "rare events" [39][40][41].…”

Section: Introductionmentioning

confidence: 99%

Molecular dynamics modeling of the sub-THz vibrational absorption of thioredoxin from E. coli

et al. 2011

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Sub-terahertz (THz) vibrational modes of the protein thioredoxin in a water environment were simulated using molecular dynamics (MD) in order to find the conditions needed for simulation convergence, improve the correlation between experimental and simulated absorption frequencies, and ultimately enhance the predictive capabilities of computational modeling. Thioredoxin from E. coli was used as a model molecule for protocol development and to optimize the simulation parameters. The empirically parameterized software packages Amber 8 and 10 were used in this work. Using atomic trajectories from the constant energy and volume MD simulations, thioredoxin's sub-THz vibrational spectra and absorption coefficients were calculated in a quasi-harmonic approximation. An optimal production run length ~100 ps was found, in agreement with experimental data on thioredoxin relaxation dynamics. At the same time, a new procedure was developed for averaging correlation matrices of atomic coordinates in MD simulations. In particular, the open source package ptraj was edited to improve a matrix-analyzing function. Averaging only six matrices gave much more consistent results, with absorption peak intensities exceeding those from the individual spectra and a rather good correlation between simulated vibrational frequencies and experimental data.

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“…The concepts of first and second hydration shells, 34,35 water bound to flexible or fixed side-chains in wide, deep or narrow crevices, small or big cavities in the interior of the protein, 2 distribution hierarchies 36 and proximal or perpendicular radial distribution functions 5,9,37 are among many ideas put forward to link simulation and experimental evidence. Buried and tightly bound water molecules exhibit residence times of the order of hundreds of picoseconds, [38][39][40][41] whereas water molecules that are more on the surface and in contact with the bulk water exhibit shorter residence times of the order of 5-50 ps. 37,[41][42][43][44][45] The interdependence of protein surface and bound water has been analyzed carefully for 56 highresolution protein structures.…”

Section: Introductionmentioning

confidence: 99%