CoMFA of Artemisinin derivatives: effect of location and size of lattice

A CoMFA study of artemisinin derivatives with changes of the location and the number of lattice points was performed. The location of probe atoms in a large lattice has practically no effect on the cross-validated r2 value (r2cv). The selection of only 18 probe atoms around the peroxide bond, considering the action mechanism of artemisinin, provided a less time-demanding and more reliable CoMFA model, which forecasts better than the large lattice model despite the lower r2cv value. Only 1 Å displacement of the small lattice caused a reduction of cross-validated r2 value of more than 50%, which indicates the lattice location played an important role in this small lattice model.