MOLECULAR QUANTUM SIMILARITY MEASURES TUNED 3D QSAR - AN ANTITUMORAL FAMILY VALIDATION-STUDY

In this work, a new methodology to construct a tuned QSAR model is pre sented, which is based on a convex set formalism. The present procedur e continues previous 3D QSAR studies, performed using molecular quantu m similarity measures (MQSM). With this new computational tool, the ef ficiency of MQSM applied to QSAR analysis is significantly improved. A reliable QSAR model is obtained using convex linear combinations of d ifferent kinds of MQSM, corresponding to different quantum-mechanical operators related to the quantum similarity integral. The active compo unds studied here, as a case study, are a set of antitumor agents, the camptothecin molecule and analogues, and the property evaluated is th e topoisomerase-I inhibition activity. Before performing a tuned QSAR analysis with this particular molecular set, a simple QSAR study for a ll the different possible types of MQSM is carried out. In addition, a nother application of MQSM is presented, to determine which method can be used to optimize molecular structures in order to reproduce experi mental molecular geometries as well as possible.