R-group template CoMFA combines benefits of "ad hoc" and topomer alignments using 3D-QSAR for lead optimization

Template CoMFA methodologies extend topomer CoMFA by allowing user-designated templates, for example the experimental receptor-bound conformation of a prototypical ligand, to help determine the alignment of training and test set structures for 3D-QSAR. The algorithms that generate its new structural modality, template-constrained topomers, are described. Template CoMFA's resolution of certain topomer CoMFA concerns, by providing user control of topological consistency and structural acceptability, is demonstrated for sixteen 3D-QSAR training sets, in particular the Selwood dataset.