A general model for predicting the binding affinity of reversibly and irreversibly dimerized ligands.

ABSTRACT: Empirical data has shown that bivalent inhibitors can bind a given target protein significantly better than their monomeric counterparts. However, predicting the corresponding theoretical fold improvements has been challenging. The current work builds off the reacted-site probability approach to provide a straightforward baseline reference model for predicting fold-improvements in effective affinity of dimerized ligands over their monomeric counterparts. For the more familiar irreversibly linked bivalents, the model predicts a weak dependence on tether length and a scaling of the effective affinity with the 3/2 power of the monomer's affinity. For the previously untreated case of the emerging technology of reversibly linking dimers, the effective affinity is also significantly improved ove

SUBMITTER: Foreman KW 

PROVIDER: S-EPMC5699851 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature