A New Pharmacophore Model for the Design of Sigma-1 Ligands Validated on a Large Experimental Dataset.

ABSTRACT: The recent publication of the σ1R crystal structure is an important cornerstone for the derivation of more accurate activity prediction models. We report here a comparative study involving a set of more than 25,000 structures from our internal database that had been screened for σ1R affinity. Using the recently published crystal structure, 5HK1, two new pharmacophore models were generated. The first one, 5HK1-Ph.A, was obtained by an algorithm that identifies the most important receptor-ligand interactions including volume restrictions enforced by the atomic structure of the recognition site. The second, 5HK1-Ph.B, resulted from a manual edition of the first one by the fusion of two hydrophobic (HYD) features. Finally, we also docked the database using a high throughput docki

SUBMITTER: Pascual R 

PROVIDER: S-EPMC6555132 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature