MIMIC - A MOLECULAR-FIELD MATCHING PROGRAM - EXPLOITING APPLICABILITYOF MOLECULAR SIMILARITY APPROACHES

This contribution presents the development and applicability of MIMIC, a molecular-field matching program for quantitatively evaluating the similarity between molecules, in a computationally feasible way and as sesses the relative orientation that maximizes their similarity. In th e present version one can deal with two types of molecular-field simil arities, namely steric volume and electrostatic, as well as a combined similarity that takes into account a given contribution from each of them. Besides optimization of the relative spatial orientation by maxi mizing these similarities, MIMIC can perform exhaustive searches to lo cate a global similarity maximum candidate and the set of local simila rity maxima closest to it. The high accuracy of the approach permits e valuation of the similarity space coverage of each similarity maximum. In addition, the study of the relationships among similarity spaces i s proposed as a strategy to better understand the linkage between the different molecular overlay solutions obtained from the use of differe nt molecular-field representations. Finally, calculation of the atomic contributions to the total molecular similarity provides a means for locating maximum similarity loci and for constructing pharmacophore pa tterns. The methodological bases and a detailed description of how the y were implemented in MIMIC to handle molecular matchings between larg e systems is presented. All current features of the program were appli ed to a relative ligand-binding problem between two nonnucleoside HIV- 1 reverse transcriptase inhibitors. (C) 1997 by John Wiley & Sons, Inc .