Sunday, June 19, 2011



Although no single drug has been designed solely by computer techniques, the contribution of these methods to drug discovery is no longer a matter of dispute.  All the world’s major pharmaceutical and biotechnology companies use computational design tools.  At their lowest level the contributions represent the replacement of  crude mechanical models by  displays of  structure which are a much more accurate reflection  of  molecular  reality, capable  of  demonstrating motion  and solvent effects.  Beyond  this, theoretical calculations permit the  computation of  binding  free energies and other relevant molecular properties.  The theoretical tools include empirical molecular mechanics, quantum mechanics and, more recently,  statistical  mechanics.  This latest advance has permitted explicit solvent effects to be incorporated.  Underpinning all this work is the availability of  high quality computer graphics, largely supported on workstations.
Two distinct categories of research are clearly distinguishable:
crystallography, nmr or homology modelling.
A detailed molecular structure of the target macromolecule, the drug receptor, is known from x-ray
variable activity of otherwise similar molecules.
The target receptor binding site has properties which can only be inferred from a knowledge of the both these types of approach will now be considered and illustrated with some recent examples.

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