Environment and exposure to solvent of protein atoms. Lysozyme and insulin

Shrake, Andrew; Rupley, John A.

doi:10.1016/0022-2836(73)90011-9

Cited by 1,228 publications

(819 citation statements)

References 8 publications

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“…Discretization methods are numerical methods relying on analysis of grid points or uniformly spaced dots for identification and quantification of volume and area. For example, several methods place dots on the surface of atoms at a distance equal to the van der Waals plus probe radii, and surface components are then derived from the collection of these dots (Shrake & Rupley, 1973;Rashin et al, 1986). Alternatively, a volume box containing the protein is divided into cubic grids, and the collection of the grid points that lie outside any atom is processed for identification and quantification of cavities and pockets (Voorintholt et al, 1989;Ho & Marshall, 1990;Delaney, 1992;Kleywegt & Jones, 1994).…”

Section: Comparison Of Cast To Other Methods For Characterizing Protementioning

confidence: 99%

Anatomy of protein pockets and cavities: Measurement of binding site geometry and implications for ligand design

1998

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Identification and size characterization of surface pockets and occluded cavities are initial steps in protein structurebased ligand design. A new program, CAST, for automatically locating and measuring protein pockets and cavities, is based on precise computational geometry methods, including alpha shape and discrete flow theory. CAST identifies and measures pockets and pocket mouth openings, as well as cavities. The program specifies the atoms lining pockets, pocket openings, and buried cavities; the volume and area of pockets and cavities; and the area and circumference of mouth openings. CAST analysis of over 100 proteins has been carried out; proteins examined include a set of SI monomeric enzyme-ligand structures, several elastase-inhibitor complexes, the pockets and cavities in protein crystal structures and quantifying their size. The method is a computational geometry treatment of complex shapes, based on alpha shape and discrete flow theory, and a related suite of programs,

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Section: Comparison Of Cast To Other Methods For Characterizing Protementioning

confidence: 99%

Anatomy of protein pockets and cavities: Measurement of binding site geometry and implications for ligand design

1998

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“…83 The method is general and includes also internal cavities in the protein which enables to account for hydrogen bonding by internal water molecules. For each atomic SAS to be computed, 1000 test points were approximately evenly distributed on a sphere centered on the atom of interest and with a radius equal to the sum of the van der Waals radius and the water solvent probe radius of 1.4Å.…”

Section: Simulation Protocolmentioning

confidence: 99%

Optimization of Model Parameters for Describing the Amide I Spectrum of a Large Set of Proteins

2012

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A new simulation protocol for the prediction of the infrared absorption of the amide I vibration of proteins was developed. The method incorporates known effects on the intrinsic frequencies (backbone conformation, inter-peptide and peptide-solvent hydrogen bonding) and couplings (nearest neighbor coupling, transition dipole coupling) of amide I oscillators in a parametrized manner. Model parameters for the simulation of amide I spectra were determined through fitting and optimization of simulated spectra to experimentally measured infrared spectra of 44 proteins that represent maximum structural variation in terms of different folds and secondary structure contents. Prediction of protein spectra using the optimized parameters resulted in good agreement with experimental spectra and in a considerable improvement compared to a description involving only transition dipole coupling.

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“…Specific mutations at the first 3 sites led to greatly reduced thermal hysteresis activities when compared to wild-type QAE. Of Surface accessibility is the ratio between the calculated accessible surface area of a side chain in the NMR structure of Type 111 AFP and the surface area of the side chain in random coil (Shrake & Rupley, 1973).…”

Section: Site-directed Mutagenesis Of Residues On the C-terminal P-sheetmentioning

confidence: 99%

Structure‐function relationship in the globular type III antifreeze protein: Identification of a cluster of surface residues required for binding to ice

et al. 1994

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Antifreeze proteins (AFPs) depress the freezing point of aqueous solutions by binding to and inhibiting the growth of ice. Whereas the ice-binding surface of some fish AFPs is suggested by their linear, repetitive, hydrogen bonding motifs, the 66-amino-acid-long Type 111 AFP has a compact, globular fold without any obvious periodicity. In the structure, 9 P-strands are paired to form 2 triple-stranded antiparallel sheets and 1 double-stranded antiparallel sheet, with the 2 triple sheets arranged as an orthogonal &sandwich (Sonnichsen FD, Sykes BD, Chao H, Davies PL, 1993, Science 2591154-1157). Based on its structure and an alignment of Type 111 AFP isoform sequences, a cluster of conserved, polar, surface-accessible amino acids (N14, T18, 444, and N46) was noted on and around the triple-stranded sheet near the C-terminus. At 3 of these sites, mutations that switched amide and hydroxyl groups caused a large decrease in antifreeze activity, but amide to carboxylic acid changes produced AFPs that were fully active at pH 3 and pH 6. This is consistent with the observation that Type 111 AFP is optimally active from pH 2 to pH 11. At a concentration of 1 mg/mL, Q44T, N14S, and T18N had 50'70, 25%, and 10% of the activity of wild-type antifreeze, respectively. The effects of the mutations were cumulative, such that the double mutant N14S/Q44T had 10% of the wild-type activity and the triple mutant N14S/T18N/Q44T had no activity. All mutants with reduced activity were shown to be correctly folded by NMR spectroscopy. Moreover, a complete characterization of the triple mutant by 2-dimensional NMR spectroscopy indicated that the individual and combined mutations did not significantly alter the structure of these proteins. These results suggest that the C-terminal @-sheet of Type 111 AFP is primarily responsible for antifreeze activity, and they identify N14, T18, and 444 as key residues for the AFP-ice interaction.Keywords: NMR; site-directed mutagenesis; thermal hysteresis Some cold water marine fishes produce proteins or glycoproteins that lower the freezing point of their blood without significantly increasing its osmolarity (DeVries, 1983;Davies & Hew, 1990). These antifreeze proteins or glycoproteins bind to and halt the growth of seed ice crystals that form in solution at or below Reprint requests to: Peter L. Davies, Department of Biochemistry, Queen's University, Kingston, Ontario K7L 3N6, Canada.Abbreviations: AFGP, antifreeze glycoprotein; AFP, antifreeze protein; FPLC, fast protein liquid chromatography; H bond, hydrogen bond; NOESY, nuclear Overhauser effect spectroscopy; QAE, quaternary aminoethyVAFP isoform that binds QAE-Sephadex; TOCSY, total correlation spectroscopy; lD, one-dimensional; 2D, two-dimensional; 3D, three-dimensional.

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Environment and exposure to solvent of protein atoms. Lysozyme and insulin

Cited by 1,228 publications

References 8 publications

Anatomy of protein pockets and cavities: Measurement of binding site geometry and implications for ligand design

Anatomy of protein pockets and cavities: Measurement of binding site geometry and implications for ligand design

Optimization of Model Parameters for Describing the Amide I Spectrum of a Large Set of Proteins

Structure‐function relationship in the globular type III antifreeze protein: Identification of a cluster of surface residues required for binding to ice

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