Simulations of a G protein‐coupled receptor homology model predict dynamic features and a ligand binding site
2008; Wiley; Volume: 582; Issue: 23-24 Linguagem: Inglês
10.1016/j.febslet.2008.08.022
ISSN1873-3468
AutoresSteffen Wolf, Marcus Böckmann, Udo Höweler, Jürgen Schlitter, Klaus Gerwert,
Tópico(s)Protein Structure and Dynamics
ResumoA computational approach to predict structures of rhodopsin‐like G protein‐coupled receptors (GPCRs) is presented and evaluated by comparison to the X‐ray structural models. By combining sequence alignment, the rhodopsin crystal structure, and point mutation data on the β 2 adrenoreceptor (b2ar), we predict a (−)‐epinephrine‐bound computational model of the β 2 adrenoreceptor. The model is evaluated by molecular dynamics simulations and by comparison with the recent X‐ray structures of b2ar. The overall correspondence between the predicted and the X‐ray structural model is high. Especially the prediction of the ligand binding site is accurate. This shows that the proposed dynamic homology modelling approach can be used to create reasonable models for the understanding of structure and dynamics of other rhodopsin‐like GPCRs.
Referência(s)