title: Ab initio modeling and molecular dynamics simulation of the alpha 1b-adrenergic receptor activation.
abstract: This work describes the ab initio procedure employed to build an activation model for the alpha 1b-adrenergic receptor (alpha 1b-AR). The first version of the model was progressively modified and complicated by means of a many-step iterative procedure characterized by the employment of experimental validations of the model in each upgrading step. A combined simulated (molecular dynamics) and experimental mutagenesis approach was used to determine the structural and dynamic features characterizing the inactive and active states of alpha 1b-AR. The latest version of the model has been successfully challenged with respect to its ability to interpret and predict the functional properties of a large number of mutants. The iterative approach employed to describe alpha 1b-AR activation in terms of molecular structure and dynamics allows further complications of the model to allow prediction and interpretation of an ever-increasing number of experimental data.
authors.affiliation: Dipartimento di Chimica, Università di Modena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Fanelli
authors.forename: C
authors.initials: C
authors.lastname: Menziani
authors.forename: A
authors.initials: A
authors.lastname: Scheer
authors.forename: S
authors.initials: S
authors.lastname: Cotecchia
authors.forename: P G
authors.initials: PG
authors.lastname: De Benedetti
mesh_terms: D000595:Amino Acid Sequence; D001436:Bacteriorhodopsins / Q000737:chemistry; D003198:Computer Simulation; D019204:GTP-Binding Proteins / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D016296:Mutagenesis; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D055672:Static Electricity
chemical_list: D018340:Receptors, Adrenergic, alpha-1; D001436:Bacteriorhodopsins; D012243:Rhodopsin; D019204:GTP-Binding Proteins