On homology modeling of the M₂ muscarinic acetylcholine receptor subtype.

ABSTRACT: Twelve homology models of the human M2 muscarinic receptor using different sets of templates have been designed using the Prime program or the modeller program and compared to crystallographic structure (PDB:3UON). The best models were obtained using single template of the closest published structure, the M3 muscarinic receptor (PDB:4DAJ). Adding more (structurally distant) templates led to worse models. Data document a key role of the template in homology modeling. The models differ substantially. The quality checks built into the programs do not correlate with the RMSDs to the crystallographic structure and cannot be used to select the best model. Re-docking of the antagonists present in crystallographic structure and relative binding energy estimation by calculating MM/GBSA in Prime and

SUBMITTER: Jakubik J 

PROVIDER: S-EPMC3717152 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature