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.