Binding affinities controlled by shifting conformational equilibria: opportunities and limitations.
Biophys J
; 108(10): 2585-2590, 2015 May 19.
Article
em En
| MEDLINE
| ID: mdl-25992736
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Ubiquitina
/
Simulação de Dinâmica Molecular
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Biophys J
Ano de publicação:
2015
Tipo de documento:
Article