8 February 2019
3D Quantitative Structure-Activity Relationship
Structure-Based and Ligand-Based 3D QSARs
The 3D QSAR method is categorized to the structure-based and ligand-based manners, respectively.
The structure-based 3D QSAR is only available for the case where the 3D structures of a target protein or its homologue bound to the active compound has been experimentally solved using the X-ray crystal structure analysis.
When a homology-modeled target protein is used for this purpose, the numerous combinations of the side chain rotamers in the ligand-binding site must be considered in order to obtain a linear relationship between the in vitro activity of the compounds and the interaction energy (or score) of the complexes.
On the other hand, the ligand-based 3D QSAR is useful, when a fine 3D structure of the target protein are not known experimentally.
Moreover, if a linear relationship is given from the ligand-based 3D QSAR, a receptor image obtained from the superposed structures is mapped by the pharmacophore characteristics of the active compounds, and this receptor image can be further used for the docking study.