What exactly are 4-D, 5-D and 6-D QSAR ?
The fourth dimension in 4-D QSAR is the possibility to represent each molecule by an ensemble of conformations, orientations, and protonation states – thereby significantly reducing the bias associated with the choice of the ligand alignment. The most likely bioactive conformation/alignment is identified by the genetic algorithm. See, for example, J.Med.Chem. 2000, 43, 4416–4427 The fifth dimension in 5-D QSAR is the possibility to represent an ensemble of up to six different induced-fit models. The model yielding the highest predictive surrogates is selected during the simulated evolution. Cf. J.Med.Chem. 2002, 45, 2139–2149. 6D-QSAR allows for the simultaneous evaluation of different solvation models. Details can be found in J.Med.Chem.
