title: Automated generation of turn mimetics: proof of concept study for the MC4 receptor.
abstract: An algorithm has been devised for the automatic design of peptide turn mimetics, particularly applicable to peptide-activated GPCRs. The method is based on flexible alignments using a new design paradigm and scoring system that aims to reduce the molecular weight of the compound and preferentially lead to drug like molecules. The process can be applied either as a de novo design or a virtual screening tool. Its use has been demonstrated by the design of novel double digit nanomolar ligands for the melanocortin 4 receptor (MC4). The method is, in principle, applicable to any type of receptor, including orphan receptors.
authors.affiliation: Neurocrine Biosciences, 12790 El Camino Real, San Diego, CA 92130, USA.
authors.forename: J Christian
authors.initials: JC
authors.lastname: Baber
authors.forename: Richard
authors.initials: R
authors.lastname: Lowe
authors.forename: John
authors.initials: J
authors.lastname: Saunders
authors.forename: Miklos
authors.initials: M
authors.lastname: Feher
mesh_terms: D000465:Algorithms; D002460:Cell Line; D002851:Chromatography, High Pressure Liquid; D039301:Computers, Molecular; D015195:Drug Design; D006801:Humans; D008024:Ligands; D018716:Molecular Mimicry; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011759:Pyrrolidines / Q000737:chemistry; D044105:Receptor, Melanocortin, Type 4 / Q000737:chemistry / Q000378:metabolism; D014584:User-Computer Interface
chemical_list: D008024:Ligands; C470072:MC4R protein, human; D019151:Peptide Library; D010455:Peptides; D011759:Pyrrolidines; D044105:Receptor, Melanocortin, Type 4