Importance of Alignment in Developing 3-D QSAR Models of 1,5-Diaryl Pyrazoles for Prediction of COX-2 Inhibitory Activity

Internet Electron. J. Mol. Des. 2003, 1, 000–000 Abstract Motivation. A set of thirty-four 1,5-diaryl pyrazoles having selective COX-2 inhibitory activity were analyzed using Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA). One of the important steps in CoMFA is the derivation of active conformation and alignment of molecules. The success of CoMFA depends on the relative positioning of the ligands in the fixed lattice, prior to generation of the 3-D descriptors. Thus, we performed two different alignments such as as_is database alignment and the alignment based on FlexX docking. The first method is based solely on the selection of ligand atoms and the second method involves protein based docking and use of the docked conformations.