In this context, electronic structure methods constitute a precious (and almost exclusive) source of information on biochemically-relevant noncovalent interactions between individual molecules -which, in turn, often used for the parametrization and calibration of more approximate computational modeling techniques (such as classical molecular mechanics force fields). Having been involved in a few recent quantum chemical investigations of noncovalent complexes, we shall now attempt to employ B3LYP/TZVP calculationswhich have been shown to be capable of providing reliable noncovalent interaction energetics -for the purpose of calculating energy differences associated with the aforementioned substitutions. In such manner, reliable energetic "gains/losses" which result from these particular substitutions may be quantitatively assessed, so that important practical conclusions regarding the above prediction may be drawn. This general strategy is concisely summarized in Figure .