title: A virtual screening study of the acetylcholine binding protein using a relaxed-complex approach.
abstract: The nicotinic acetylcholine receptor (nAChR) is a member of the ligand-gated ion channel family and is implicated in many neurological events. Yet, the receptor is difficult to target without high-resolution structures. In contrast, the structure of the acetylcholine binding protein (AChBP) has been solved to high resolution, and it serves as a surrogate structure of the extra-cellular domain in nAChR. Here we conduct a virtual screening study of the AChBP using the relaxed-complex method, which involves a combination of molecular dynamics simulations (to achieve receptor structures) and ligand docking. The library screened through comes from the National Cancer Institute, and its ligands show great potential for binding AChBP in various manners. These ligands mimic the known binders of AChBP; a significant subset docks well against all species of the protein and some distinguish between the various structures. These novel ligands could serve as potential pharmaceuticals in the AChBP/nAChR systems.
authors.affiliation: Department of Chemistry & Biochemistry, University of California at San Diego, 9500 Gilman Dr MC 0365, La Jolla, CA 92093-0365, USA.
authors.forename: Arneh
authors.initials: A
authors.lastname: Babakhani
authors.forename: Todd T
authors.initials: TT
authors.lastname: Talley
authors.forename: Palmer
authors.initials: P
authors.lastname: Taylor
authors.forename: J A
authors.initials: JA
authors.lastname: McCammon
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D019295:Computational Biology; D008024:Ligands; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D011978:Receptors, Nicotinic / Q000737:chemistry / Q000378:metabolism
chemical_list: C428944:AChBP protein, Lymnaea; D002352:Carrier Proteins; D008024:Ligands; D011978:Receptors, Nicotinic