Field interaction and geometrical overlap: A new simplex and experimental design based computational procedure for superposing small ligand molecules

Alignment of molecules is a crucial and time-consuming step in any 3D-QSAR study. For this reason, the field interaction and geometrical overlap (FIGO) procedure presented in this paper is particularly relevant because it can provide an objective and automatic superposition of ligands through the computation of an appropriate alignment index (AI). Ligand overlay takes place via a simplex optimization of the AI function. Experimental design strategies (full factorial design, D-optimal design) are used to define the starting positions of the superposing molecules. Overlay experiments are carried out to test the performance of the method. Comparison between the results obtained with FIGO and known ligand-receptor X-ray crystallographic data (Protein Data Bank) suggests that FIGO is an effective and reliable computational procedure.