Determination of the conformational states of strychnine in solution using NMR residual dipolar couplings in a tensor-free approach.
Methods
; 148: 4-8, 2018 09 15.
Article
en En
| MEDLINE
| ID: mdl-30036639
ABSTRACT
Small molecules with rotatable bonds can occupy different conformational states in solution as a consequence of their thermal fluctuations. The accurate determination of the structures of such states, as well as of their statistical weights, has been challenging because of the technical difficulties in extracting information from experimental measurements, which are normally averaged over the conformational space available. Here, to achieve this objective, we present an approach based on a recently proposed tensor-free method for incorporating NMR residual dipolar couplings as structural restraints in replica-averaged molecular dynamics simulations. This approach enables the information provided by the experimental data to be used in the spirit of the maximum entropy principle to determine the structural ensembles of small molecules. Furthermore, in order to enhance the sampling of the conformational space we incorporated the metadynamics method in the simulations. We illustrate the method in the case of strychnine, determining the three major conformational states of this small molecule and their associated occupation probabilities.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Estricnina
/
Resonancia Magnética Nuclear Biomolecular
/
Simulación de Dinámica Molecular
/
Conformación Molecular
Idioma:
En
Revista:
Methods
Asunto de la revista:
BIOQUIMICA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Reino Unido