| Abstract
| - Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure−activityrelationship (3D-QSAR) technique, has proven to be a valuable tool in the field of rational drug design. Inits native form, CoMFA utilizes a pseudoreceptor, in the form of a regularly spaced lattice of probe atoms,to characterize the steric and electrostatic properties of a series of mutually superimposed molecules. Statisticalanalyses are performed in an attempt to correlate changes in these shape and charge related fields to observeddifferences in biological activities at a given target. Graphical analyses of the resulting “negative receptorimages” have been demonstrated to provide insight into the physicochemical requirements of novel ligands.Several groups have previously demonstrated the benefits of additional or alternative fields for these typesof analyses. In this report, a novel molecular potential field derived from atomistic contributions to molecularpolarizability is presented. Comparison studies will be presented using literature data sets and CoMFAmodels derived from steric, electrostatic, and polarizability fields. The overall conclusion is that molecularpolarizability fields derived from semiempirically determined atomic polarizabilities are highly predictiveand graphically descriptive supplements to, and perhaps surrogates for, the standard CoMFA steric andelectrostatic fields.
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