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Biomedical subjects

J A Schellman

Publications and source records attributed to J A Schellman.

At least 37 records · Page 2Linked to original sources
PubMed1980

The flexibility of DNA. I. Thermal fluctuations.

The theory of the flexibility of DNA makes use of a worm-like coil model which implies an isotropic bending potential. This paper investigates the influence of non-isotropic bending which is cased by the real, lower symmetry of a DNA molecule. Formulas are developed for the persistence and mean square length of a molecule in terms of DNA symmetry elements, i.e., a helical screw operation and perpendicular dyad axes. It is shown that the low symmetry of a DNA helix leads to mean propagation properties which differ from the static equilibrium properties. The worm-like coil model may be justified in terms of the mean, thermally averaged, properties of the DNA but not in terms of its equilibrium properties. Changes in helix angle and displacement with temperature and solvent are a natural result of the asymmetric potential of DNA.

Base Composition↗
PubMed1980

The flexibility of DNA. II. Spontaneous and ligand induced distortions.

DNA can bend not only as a result of smooth worm-like deviations from linearity, but also in an abrupt fashion because of natural spontaneous fluctuations in structure (breathing modes, kinks, etc.) and because its interaction with other molecules (dyes, proteins, other ligands). It is shown how all these structural deformations can be treated with a single geometrical model and the statistical theory of such deformations is developed into specific formulas for persistence and mean directions. The statistical theory does not apply to bending which is cooperative or site specific.

Base Composition↗
PubMed1979

Stability of phage T4 lysozymes. II. Unfolding with guanidinium chloride.

The denaturation by guanidinium chloride of three phage lysozymes (wild type and two mutants) was investigated. The study of solvent denaturation permitted the investigation of the relative stabilities of the proteins at neutral pH, in contrast to thermal denaturation studies reported earlier which could only be performed in acid pH. The results were interpreted assuming that the free energy of solution of proteins is a linear function of denaturant concentration. Using standard thermodynamic formulas this permits the calculation of the stabilities of the three proteins in the absence of guanidinium chloride. The single point mutation Trp 138 leads to Tyr leads to relatively large changes in stability and the interaction of the protein with guanidinium chloride. The changes associated with the subsequent double mutation, Trp 126 leads to Tyr, Trp 158 leads to Tyr, are much smaller indicating a relatively smooth adjustment of the protein structure to the changed side chains. Models of the structural effects of point mutations are discussed. It is found that the mutation at position 138 does not fit a model in which the effect of a substitution is to introduce an energetic strain in the structure. It does fit a model in which there is a partial unravelling of the structure as a result of the mutation. However, there are no changes in the backbone circular dichroism spectra associated with the mutation. The two observations are not necessarily in conflict. Further physical studies are required for the resolution of the problem.

Guanidines↗
PubMed1977

Stability of phage T4 lysozymes. I. Native properties and thermal stability of wild type and two mutant lysozymes.

Two mutants of phage T4 lysozyme were prepared and characterized. One mutation substituted a tyrosine residue for tryptophan at position 138. The other substituted tyrosines at all three tryptophan positions of the wild type molecule (126, 138, 158). Comparative studies of the physical properties (absorption, fluorescence, circular dichroism) of the three enzymes were performed as a function of pH. Also, the proteins were reversibly melted as a function of pH. Since the unfolding reaction appeared to be a two-state process for all these proteins, the data were analyzed by the van 't Hoff procedure. The changes in stability and activity produced by substitution of Trp 138 were especially significant. The other substitutions were neutral. See the end of the paper for a summary of conclusions. In the appendix the appropriate thermodynamic relations are developed for a constant deltaCp transition.

Circular Dichroism↗