The readers' NIH.
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Financing, Government↗
Biomedical subjects
S Doniach
Publications and source records attributed to S Doniach.
A computer model to dynamically simulate protein folding: studies with crambin.
The current work describes a simplified representation of protein structure with uses in the simulation of protein folding. The model assumes that a protein can be represented by a freely rotating rigid chain with a single atom approximating the effect of each side chain. Potentials describing the attraction or repulsion between different types of amino acids are determined directly from the distribution of amino acids in the database of known protein structures. The optimization technique of simulated annealing has been used to dynamically sample the conformations available to this simple model, allowing the protein to evolve from an extended, random coil into a compact globular structure. Many characteristics expected of true proteins, such as the sequence-dependent formation of secondary structure, the partitioning of hydrophobic residues, and specific disulfide pairing, are reproduced by the simulation, suggesting the model may accurately simulate the folding process.
Computer Simulation↗
Small-angle x-ray scattering investigation of the solution structure of troponin C.
X-ray crystallographic studies of troponin C (Herzberg, O., and James, M.N.G. (1985) Nature 313, 653-659; Sundaralingam, M., Bergstrom, R., Strasburg, G., Rao, S.T., and Roychowdhury, P. (1985a) Science 227, 945-948) have revealed a novel protein structure consisting of two globular domains, each containing two Ca2+-binding sites, connected via a nine-turn alpha-helix, three turns of which are fully exposed to solvent. Since the crystals were grown at pH approximately 5, it is of interest to determine whether this structure is applicable to the protein in solution under physiological conditions. We have used small-angle x-ray scattering to examine the solution structure of troponin C at pH 6.8 and the effect of Ca2+ on the structure. The scattering data are consistent with an elongated structure in solution with a radius of gyration of approximately 23.0 A, which is quite comparable to that computed for the crystal structure. The experimental scattering profile and the scattering profile computed from the crystal structure coordinates do, however, exhibit differences at the 40-A level. A weak Ca2+-facilitated dimerization of troponin C was observed. The data rule out large Ca2+-induced structural changes, indicating rather that the molecule with Ca2+ bound is only slightly more compact than the Ca2+-free molecule.
Algorithms↗
Location of terbium binding sites on acetylcholine receptor-enriched membranes.
Acetylcholine receptor-enriched membranes bind 45 terbium cations per receptor. The Tb(III) X-ray scattering factor changes by as much as 30% over a 50 eV range about the L3 absorption edge. We exploit these changes to modulate the contribution of these ions to the X-ray diffraction pattern of oriented receptor-enriched membranes by varying the incident X-ray energy. Difference Fourier analysis of the meridional diffraction amplitudes at two X-ray energies revealed six localized regions of Tb(III) density across the membrane. Most significant is the finding of 18 Tb(III) ions near the entrance and 11 ions near the exit of the ion channel as well as 4 or 5 Tb(III) ions localized in the channel itself. This evidence strongly suggests the presence of anionic carboxylate side-chains on the channel lining.
Animals↗
Applications of X-ray photoabsorption spectroscopy to the determination of local structure in organometallic compounds.
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Absorption↗
X-ray absorption spectroscopy using synchrotron radiation for structural investigation of organometallic molecules of biological interest.
The technique of x-ray absorption spectroscopy using tuneable, very intense x-rays from a high energy electron storage ring has been applied to study of the estended x-ray absorption fine structure for Cu and Ni tetraphenylporphyrin and methemoglobin. Preliminary analysis shows that the spectra may be interpreted as a super-position of modulations arising from the nearest neighbor nitrogen and pyrrole alpha-carbon coordination sheels of the metal atoms. We estimate that with the observed magnitude of noise to modulation amplitude, relative shifts of 0,5% in the metal-nitrogen to metal-carbon bond distances in the prophyrins should be observable using extended x-ray absorption fine structure and that this technique may provide a method of observing these types of structural changes in solution.
Copper↗
The impact of intestinal biopsy on gastroenterology.
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Biopsy↗