Biomedical subjects

W E Briggs

Publications and source records attributed to W E Briggs.

7 recordsLinked to original sources

PubMed1988

Protein-ligand binding with a missing species.

Considerable experimental evidence has been produced recently that shows that in the binding of oxygen or carbon monoxide to certain tetrameric hemoglobins, the triply-ligated species is virtually non-existent. The binding polynomial representing this phenomenon for the general case is P(x) = 1 + beta 1x + ... + beta n-1xn-1 + beta nxn, where beta n-1 is nearly zero. The zeros, factorization and associated Hill plots of such binding polynomials with beta n-1 = 0 are investigated for the general case, and are analyzed in detail for n = 3 and n = 4. These results are then compared with the results obtained from experimental data on a number of tetrameric hemoglobins for which beta 3 is small. One concludes that, apart from the slope of the high-saturation asymptote of the Hill plot, a small perturbation of beta 3 from zero produces small changes in other properties associated with the binding process, such as fractional saturation, maximum Hill slope, and zeros and factorization of the binding polynomial.

Animals↗

PubMed1986

Analysis of zeros of binding polynomials for tetrameric hemoglobins.

A quantitative measure of the validity of the MWC description of cooperative binding equilibria has been obtained which uses only the Adair constants. This is accomplished through simple relationships using the zeros of the Adair binding polynomial and unique properties of the zeros of MWC polynomials as described in the accompanying paper (W.E. Briggs, Biophys. Chem. 24 (1986) 311). The method is applied to oxygen binding to a large number of hemoglobins under a wide variety of conditions. In most cases, exemplified by human hemoglobin under a wide range of conditions, the MWC model is allowed and the probability of its suitability is determined. The probability given by this method correlates directly with the deviation between the experimental binding curve and that derived from the theory. In several cases the pattern of the Adair polynomial zeros immediately excludes the MWC model, most notably for carp hemoglobins. A physical picture of cooperative binding site interactions is nevertheless obtained from the patterns of zeros as they relate to the factorization of the binding polynomial.

Animals↗

PubMed1986

A probabilistic model for fitting MWC polynomials in protein-ligand binding.

Given a binding polynomial in Adair form, A(x) = 1 + beta 1 x + ... + beta n x n, beta i greater than or equal to 0, a basic problem is to determine a method of fitting a model polynomial to A(x) and a quantitative measure of the goodness of fit. This paper presents such a method for fitting Monod-Wyman-Changeux (MWC) model polynomials when A(x) is of degree three or four. The method of fitting is based on the property that the zeros of an MWC polynomial of any degree lie on a circle in the complex plane. The parameters in the MWC model are determined so that if possible this circle coincides with the circle on which lie the zeros of A(x). The measure of goodness of fit is provided by a probabilistic model which gives the probability that a binding polynomial has its zeros on a circle on which lie the zeros of an MWC polynomial and if so, the probability that the juxtaposition of the two sets of zeros can occur by chance alone.

Kinetics↗

PubMed1985

The relationship between zeros and factors of binding polynomials and cooperativity in protein-ligand binding.

Cooperativity in the protein-ligand binding process is discussed in terms of the zeros of the binding polynomial and the corresponding possible factorizations of the binding polynomial into polynomials having non-negative coefficients. Particular attention is paid to the case in which the real parts of all zeros are negative (Hurwitz polynomial) and the case in which the binding polynomial admits no positive factorization (positive irreducible polynomial). Such factorizations are then interpreted as site linkage patterns and related to cooperativity. The possible combinations of zeros of the binding polynomials for the MWC and KNF tetrahedral, square and linear models are determined and the corresponding factorization and linkage patterns analyzed. An application and interpretation are then made for data obtained from Trout I hemoglobin.

Animals↗

PubMed1984

Cooperativity and extrema of the Hill slope for symmetric protein-ligand binding polynomials.

The relationships between cooperativity types, both macro- and microscopic, and extrema of the slope of Hill plots for symmetric binding polynomials of degrees three and four are analyzed in detail. It is shown that the Hill plot for 1 + ax + ax 2 + x3 has three extrema for a greater than 15 which occurs in the presence of totally negative microscopic cooperativity sequences. The extrema are a maximum and a pair of minima and the absolute minimum slope is shown to be 3(square root a + 1-2)/(a - 3). For a symmetric binding polynomial of degree four, necessary and sufficient conditions for three extrema of the Hill slope are derived and again it is shown that this phenomenon can occur in the presence of totally negative microscopic cooperativity sequences. An upper bound, which is an improvement on the current best bound of two, is obtained for the absolute maximum slope when a minimum and a pair of maxima occur. A lower bound for the absolute minimum slope is found when a maximum and a pair of minima occur.

Kinetics↗

PubMed1983

A new measure of cooperativity in protein-ligand binding.

An allosteric binding system consisting of a single ligand and a nondissociating macromolecule having multiple binding sites can be represented by a binding polynomial. Various properties of the binding process can be obtained by analyzing the coefficients of the binding polynomial and such functions as the binding curve and the Hill plot. The Hill plot has an asymptote of unit slope at each end and the departure of the slope from unity at any point can be used to measure the effective interaction free energy at that point. Of particular interest in detecting and measuring cooperativity are extrema of the Hill slope and its value at the half-saturation point. If the binding polynomial is symmetric, then there is an extremum of the Hill slope at the half-saturation point. This value, the Hill coefficient, is a convenient measure of cooperativity. The purpose of this paper is to express the Hill coefficient for symmetric binding polynomials in terms of the roots of the polynomial and to give an interpretation of cooperativity in terms of the geometric pattern of the roots in the complex plane. This interpretation is then applied to the binding polynomials for the MWC (Monod-Wyman-Changeux) and KNF (Koshland-Nemethy-Filmer) models.

Journal Article↗

PubMedDate not supplied

Improving productivity in the x-ray film file room.

A film filing system using color coding of the last two digits of assigned numbers was compared with a system designed around the current film file and readily available patient identifiers: name, sex, and date of examination. In the FASD system (filed alphabetically by sex and date), films are filed in time units by date of last activity and within these time units by sex and last name. The FASD system was shown to cut in half the routine work of film filing.

Efficiency↗