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Use of Binding Site Neighbor-Effect Parameters to Evaluate the Interactions between Adjacent Ligands on a Linear Lattice
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| Organization: | Dept. of Biopharmaceutical Sciences, University of California at San Francisco |
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| Journal of Molecular Biology |
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A method using binding site "neighbor-effect" parameters (NEPs) is introduced to evaluate the effects of interaction between adjacent ligands on their binding to an infinite linear lattice. Binding site overlap is also taken into account. This enables the conditional probability approach of McGhee and von Hippel to be extended to more complex situations. The general equation for the isotherm is v/L_F = S_F K_F, where v is the ratio of bound ligands to lattice residues, L_F is the free ligand concentration, S_F is the fraction of binding sites that are free, and K_F is the average association constant of a free site. Solutions are derived for three cases: symmetric ligands, and asymmetric ligands on isotropic or anisotropic lattices. For symmetric ligands there is one NEP, E, which is the ratio of the average binding affinity of a free site if the status of the lattice residue neighboring one end of the site is unspecified (left to chance) to the affinity when this residue is free (holding the other neighbor constant). Thus K_F is KE^2, where K is the affinity of an isolated site. If a site is n residues long, S_F is f ff^n-1, where f = 1 - nv is the fraction of residues that are free and ff is the conditional probability that a free residue is bordered on a given side by another free residue. The extpression for ff is 1/(1+x/E), where x is v/f, E is (1-x+[(1-x)^2 + ax omega]^1/2)/2, and omega is the co-operativity parameter. The binding of asymmetric ligrands to an isotropic lattice is described by two NEPs: the last case involves four NEPs and a bound ligand orientation parameter. For each case, the expected length distributaion of clusters of bound ligands can be calculated as a function of v. When Scatchard plots with the same intercepts and initial slope are compared, it is found that ligand asmmetry lowers the isotherm (relative to the corresponding symmetric ligand isotherm), whereas lattice anisotrpy raises it.
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protein-nucleic acid interactions, co-operativity, ligand asymmetry, lattice anistropy, cluster length distributions
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