Binding affinities controlled by shifting conformational equilibria: opportunities and limitations.

ABSTRACT: Conformational selection is an established mechanism in molecular recognition. Despite its power to explain binding events, it is hardly used in protein/ligand design to modulate molecular recognition. Here, we explore the opportunities and limitations of design by conformational selection. Using appropriate thermodynamic cycles, our approach predicts the effects of a conformational shift on binding affinity and also allows one to disentangle the effects induced by a conformational shift from other effects influencing the binding affinity. The method is assessed and applied to explain the contribution of a conformational shift on the binding affinity of six ubiquitin mutants showing different conformational shifts in six different complexes.

SUBMITTER: Michielssens S 

PROVIDER: S-EPMC4457000 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature