title: Methods for generating and applying pharmacophore models as virtual screening filters and for bioactivity profiling.
abstract: Biological effects of small molecules in an organism result from favorable interactions between the molecules and their target proteins. These interactions depend on chemical functionalities, bonds, and their 3D-orientations towards each other. These 3D-arrangements of chemical functionalities that make a small molecule active towards its target can be described by pharmacophore models. In these models, chemical functionalities are represented as so-called features. Commonly, they are obtained either from a set of active compounds or directly from the observed protein-ligand interactions as present in X-ray crystal structures, NMR structures, or docking poses. In this review, we explain the basics of pharmacophore modeling including dataset generation, 3D-representations and conformational analysis of small molecules, pharmacophore model construction, model validation, and its benefits to virtual screening and other applications.
authors.affiliation: Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular Biosciences Innsbruck - CMBI, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.
authors.forename: Anna
authors.initials: A
authors.lastname: Vuorinen
authors.affiliation: Institute of Pharmacy/Pharmaceutical Chemistry and Center for Molecular Biosciences Innsbruck - CMBI, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria. Electronic address: Daniela.Schuster@uibk.ac.at.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
mesh_terms: D000465:Algorithms; D003198:Computer Simulation; D062126:Databases, Chemical; D055808:Drug Discovery / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D008958:Models, Molecular
keywords: 3D-structures; Bioactivity predictions; Conformational models; Pharmacophore modeling; Virtual screening