Three dimensional molecular field analysis of thiomorpholine analogs of TACE inhibitors using receptor based alignment

Thiomorpholine analogs (TML) have been identified as novel class of potent tumor necrosis factor-α converting enzyme (TACE) inhibitors. A computational strategy based on molecular docking studies, followed by MFA analysis has been performed to elucidate the atomic details of the TACE/TML interactions and to identify the most important features impacting TACE inhibitory activity of TMLs. The generated MFA model resulted to be well predictive, and gave r² _test 0.723, conventional r ² 0.982 and r² _cv 0.811. The 3D-QSAR field contributions and the structural features of the TACE binding site showed a good correlation. These studies will be useful to design new TACE inhibitors with improved potency.