This study presents for the first time the 3D model of the σ1 receptor protein as
obtained from homology modeling techniques, shows the applicability of this structure to
docking-based virtual screening, defines a computational strategy to optimize the results based on
a combination of 3D pharmacophore-based docking and MM/PBSA free energy of binding
scoring, and provides evidence that these in silico models and recipes are powerful tools on which
virtual screening of new σ1 ligands can be based. In particular, the validation of the applicability of
docking-based virtual screening to homology models is of utmost importance, since no crystal
structure is available to date for the σ1 receptor, and this missing information still constitutes a
major hurdle for a rational ligand design for this important protein target.
