RT Journal Article
SR Electronic
T1 Resolving Three-State Ligand-Binding Mechanisms by Isothermal Titration Calorimetry: A Simulation Study
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 145516
DO 10.1101/145516
A1 Evgenii L. Kovrigin
YR 2017
UL http://biorxiv.org/content/early/2017/06/02/145516.abstract
AB In this paper, I theoretically analyzed ITC profiles for three-state equilibria involving ligand binding coupled to isomerization or dimerization transitions. Simulations demonstrate that the mechanisms where the free or ligand-bound protein undergoes dimerization (such that the ligand cannot bind to or dissociate from the dimer) produce very distinctive titration profiles. In contrast, profiles of the pre-existing equilibrium or induced-fit models cannot be distinguished from a simple two-state process, requiring data from additional techniques to positively identify these mechanisms.