Allosteric proteins use energy derived from ligand binding to promote a global change in conformation. The "gating" equilibrium constant of acetylcholine receptor-channels (AChRs) is influenced by ligands, mutations, and membrane voltage. We engineered AChRs to have specific values of this constant by combining these perturbations, and then calculated the corresponding values for a reference co...

The standard mathematical model for stepwise "slow-binding" enzyme inhibition (E+Iright harpoon over left harpoonEIright harpoon over left harpoonEI( *)) assumes that the initial enzyme-inhibitor complex EI is always at equilibrium with the free component species E and I. This assumption implies that the dissociation rate constant (EI-->E+I) is infinitely higher than the isomerization rate cons...

Dose-response curves for inhibitors (drugs) generally are analyzed by means of four-parameter fits, yielding IC(50), background, amplitude, and Hill coefficient. Hill coefficients not equal1 contradict 1:1 competition. If binding of substrates to proteins is a stepwise process where initial binding to initial locations (patches) leads to strong binding on defined sites, then drugs (non-endogeno...

The use of H-point curve isolation (HPCIM) and H-point standard addition methods (HPSAM) for spectrophotometric studies of complex formation equilibria are proposed. One step complex formation, two successive stepwise and mononuclear complex formation systems, and competitive complexation systems are studied successfully by the proposed methods. HPCIM is used for extracting the spectrum of comp...

To examine the signature of population expansion on genetic variability at microsatellite loci, we consider a population that evolves according to the time-continuous Moran model, with growing population size and mutations that follow a general asymmetric stepwise mutation model. We present calculations of expected allele-size variance and homozygosity at a locus in such a model for several var...