Transient binding patches: a plausible concept for drug binding.

ABSTRACT: 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-endogenous inhibitors) may bind to those presumably larger patches and need not follow a 1:1 stoichiometry for specific inhibition. This concept was translated into three computable models and successfully fitted to 1,282 phosphatase dose-response curves. The models only required four parameters, namely, the equilibrium dissociation constant K (D)(1) of the first inhibitor binding step, background, amplitude

SUBMITTER: Prinz H 

PROVIDER: S-EPMC2698315 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature