Modeling of the OX1R-orexin-A complex suggests two alternative binding modes.

ABSTRACT:

Background

Interactions between the orexin peptides and their cognate OX1 and OX2 receptors remain poorly characterized. Site-directed mutagenesis studies on orexin peptides and receptors have indicated amino acids important for ligand binding and receptor activation. However, a better understanding of specific pairwise interactions would benefit small molecule discovery.

Results

We constructed a set of three-dimensional models of the orexin 1 receptor based on the 3D-structures of the orexin 2 receptor (released while this manuscript was under review), neurotensin receptor 1 and chemokine receptor CXCR4, conducted an exhaustive docking of orexin-A16-33 peptide fragment with ZDOCK and RDOCK, and analyzed a total of 4301 complexes through multidimensional scaling and clusteri

SUBMITTER: Karhu L 

PROVIDER: S-EPMC4469407 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature