All-Orientation Search and All-Placement Search in Comparative Molecular Field Analysis

Three sets of molecules have been used to study the conventional CoMFA procedure. For all the three test sets, the resulting q2 values were observed to vary simply because of the change in the orientation or placement of the aligned molecules. The reason is believed to root in the imperfect sampling of the molecular field. We have introduced two new strategies, all-orientation search (AOS) and all-placement search (APS), to optimize the sampling process. By rotating and translating the molecular aggregate within the grid systematically, all the possible samplings of the molecular field are tested and subsequently the one with the highest q2 value can be picked out. We have also demonstrated that the combined application of AOS/APS with GOLPE procedure can yield results better than the ones by using them respectively.