Biomedical subjects

W R Krigbaum

Publications and source records attributed to W R Krigbaum.

4 recordsLinked to original sources

PubMed1979

Local interactions as a structure determinant for protein molecules: II.

Van der Waals interactions between sidechains are indicated to be important in determining the native state of the proteins of known structure by the following observations: 1. the average radial distribution of polarity increases continuously from the center of the molecule to its periphery. 2. nonpolar sidechains tend to occur in clusters. 3. the frequencies of long-range nearest-neighbor pairs are markedly non-random; each type of sidechain seeks nearest-neighbors of similar polarity. To investigate how these interactions affect the overall structure of the protein molecule, three simplified models are treated: a sheath-core model composed of independent residues, a modification accounting approximately for the connected nature of the chain, and a model consisting of three concentric spherical phases.

Amino Acids↗

PubMed1979

Local interactions as a structure determinant for protein molecules: III.

Investigation of the known protein structures has led to the generalization that the native folding permits each sidechain to select those nearest-neighbors which maximize stabilization from van der Waals interactions. With regard to secondary structure: 1. Helical and beta regions exhibit characteristic patterns of short-range contacts (residue numbers k and k + t with [t] less than or equal to 4) due to the geometries of these secondary structures. However, these are not strictly obligatory, and preferred short-range contacts which would result in unfavorable van der Waals interactions are replaced by favorable long-range contacts. 2. The generalization mentioned at the outset holds for individual proteins, both for short-range and long-range contacts, and without regard for the type or amount of secondary structure present. 3. These observations imply that van der Waals interactions arising from short-range contacts partially determine secondary structure, and this is demonstrated by tests based upon assignment of regions of secondary structure in the known proteins. The principle of optimizing van der Waals stabilization from long-range contacts is applied to predict the structure of the complex formed by the S-peptide and S-protein of ribonuclease-S. The formation of favorable pairs is found to be more important than the total number of intermolecular contacts, and 40 to 50% of this stabilization is contributed by two residues of the S-peptide, Phe-8 and Met-13.

Computers↗

PubMed1975

Molecular conformation of bovine A1 basic protein, a coiling macromolecule in aqueous solution.

Aqueous solutions of bovine A1 protein, the major component of the basic protein fraction of myelin, were studied by small angle X-ray diffraction. The experimentally determined molecular weight, 17,800, is within 3% of that corresponding to the amino acid sequence, 18, 395, and the radius of gyration was found to be 46.3 A. No equivalent scattering particle of uniform electron density could be found which was compatible with all parameters evaluated from the diffraction measurements. The possibility of a coiled shape was therefore investigated using a worm-like chain model. This yielded a contour length of 439 A and a persistence length of 15.7 A. The radius of gyration of this model chain, 47.1 A, is in quite reasonable accord with the experimental value. The latter, after correction for excluded volume effects and finite chain length, yields for the characteristic ratio, ro2/nplp-2, 5.4. This may be compared with the value, 6.1, obtained after applying a correction for finite chain length to the viscosity data given by Tanford et al. for 12 proteins in 6 M guanidine hydrochloride and 0.1 M beta-mercaptoethanol. These two experimental values fall in the expected order, since the 15% glycine content of the A1 protein is considerably higher than the average for other proteins, which is about 8%. The corresponding values predicted from conformational calculations by Miller et al. for random copolymers of the L-alanine-glycine type are 5.9 (18% glycine) and 7.0 (8% glycine). We conclude that the A1 protein exists predominately, if not exclusively, as a random coil in aqueous solution.

Animals↗

PubMedDate not supplied

Model membranes for the study of active transport phenomena.

Models for active transport are prepared by the covalent bonding of molecules containing a catalytic site to the membrane asymmetrically with respect to its thickness. The membrane separates two compartments of unequal volume, both initially containing reactant at the same concentration. We observed the time dependence of the reactant and product concentrations, and of the osmotic pressure, and these results are compared with theoretical predictions. The two reactions studied are the hydrolysis of ethyl N-acetyl-L-tyrosinate catalyzed by alpha-chymotrypsin and the acid-catalyzed hydrolysis of triethoxymethane. The asymmetric membrane consumes reactant, and discharges product, at different rates through its two faces. The concentration of products, and of non-rate determining reactants, may exhibit maxima or minima with time, and computer simulation indicates that oscillatory behavior could be expected under appropriate conditions. Due to the different exit path lengths, the osmotic response (determined by the solute concentrations at the two membrane surfaces) may be opposite in sign to that expected from the concentrations in the external compartments.

Biological Transport, Active↗