PT  - JOURNAL ARTICLE
AU  - Evgenii L. Kovrigin
TI  - Resolving Three-State Ligand-Binding Mechanisms by Isothermal Titration Calorimetry: A Simulation Study
AID  - 10.1101/145516
DP  - 2017 Jan 01
TA  - bioRxiv
PG  - 145516
4099  - http://biorxiv.org/content/early/2017/06/02/145516.short
4100  - http://biorxiv.org/content/early/2017/06/02/145516.full
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.