The development of a new tailor-made scoring function to predict binding affinities of protein-ligand complexes is described. Knowledge-based pair-potentials are specifically adapted to a particular protein by considering additional ligand-based information. The formalism applied to derive the new function is similar to the well-known CoMFA approach, however, the fields used in the approach originate from the protein environment (and not from the aligned ligands as in CoMFA, thus, a "reverse" CoMFA (= AFMoC) named Adaptation of Fields for Molecular Comparison is performed). A regular-spaced grid is placed into the binding site and knowledge-based pair-potentials between protein atoms and ligand atom probes are mapped onto the grid intersections resulting in "potential fields". By multiplying distance-dependent atom-type properties of actual ligands docked into the binding site with the neighboring grid values, "interaction fields" are produced from the original "potential fields". In a PLS analysis, these atom-type specific interaction fields are correlated to the actual binding affinities of the embedded ligands, resulting in individual weighting factors for each field value. As in CoMFA, the results of the analysis can be interpreted in graphical terms by contribution maps, and binding affinities of novel ligands are predicted by applying the derived 3D QSAR equation. The scope of the new method is demonstrated using thermolysin and glycogen phosphorylase b as test examples. Impressive improvements of the predictive power for affinity prediction can be achieved compared to the application of the original knowledge-based potentials by considering a sample set of only 15 known training ligands. Thus, with growing information about the drug target studied, the new method allows one to move gradually from generally valid to protein-specifically adapted pair-potentials, depending on the amount of training information available and its degree of structural diversity. In addition, convincing predictive power is also achieved for ligand poses generated by automatic docking tools.