Brief survey of scope and limitations of quantum and statistical mechanical methods

An attempt is made to delineate the scope and limitations, and future perspectives, of the theoretical methods being applied increasingly to various aspects of drug design and associated problems. The two methods of approach, quantum mechanics and statistical physics (Monte Carlo, Molecular Dynamics), are used to evaluate such properties as electron density distribution, structure and conformation, intermolecular interactions, etc. for isolated molecules and their autoassociates, and for interactions with the environment (e.g., solvent, receptor molecules). The validity of such calculations, dependent on factors such as geometrical optimalization, correlation energy and differing approximations of the form of the wave function, is illustrated in the case of enol-keto tautomerism of nitrogen heterocycles, relevant to the biological (including chemotherapeutic) activities of some nucleoside analogues. Intermolecular interactions, including the role of solvent, are assessed for purine and pyrimidines. The scope of the Molecular Dynamics methods is exemplified by its application to the mode of action of lysozyme.