Elsevier

Methods

Volume 14, Issue 3, March 1998, Pages 302-317
Methods

Regular Article
Ab InitioModeling and Molecular Dynamics Simulation of the α1b-Adrenergic Receptor Activation

https://doi.org/10.1006/meth.1998.0586Get rights and content

Abstract

This work describes theab initioprocedure employed to build an activation model for the α1b-adrenergic receptor (α1b-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 α1b-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 α1b-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.

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