Theoretical Chemistry as Part of the Interdisciplinary Approach to Rational Drug Design

Abstract

The early days of applied computational chemistry were characterized by two extreme attitudes, best represented by E. Clementi’ s enthusiastic statement in 1973 “We can calculate everything!” and C. Coulson’s reply “Give us insight not numbers!” A further decade was needed to convincingly demonstrate that computational methods can contribute significantly to real problems in organic chemistry. Theoretical methods now provide an invaluable tool to rationalize many aspects of chemical reactivity. As a consequence of the enormous developments in hardware and software, quantum mechanical calculations with a fairly high degree of sophistication can now be applied relatively easy even to series of medium-sized organic molecules such as steroids. For drug design the developments in computer graphics certainly played the decisive role to visualize molecular properties and to communicate theoretical results to the experimentalists. The potential of molecular modeling techniques as an inspiring tool to create new and unconventional ideas has now widely been recognized The contributions from computational chemistry can guide a drug finding process into areas of new (lead) structures. However, no one discipline ever produces a drug, so computational chemists cannot either. Among other areas such as synthetic chemistry, pharmacology, and biology, computational chemistry is one part of the interdisciplinary approach in the early stages of developing a drug.