Computational mechanics pharmaceutical applications

Molecular mechanics is a useful and reliable computational method for structure, energy, and other molecular properties. The mathematical basis for molecular models in MM3 has been described, along with the limitations of the method. One of the major difficulties associated with molecular mechanics, in general, and MM3 in particular is the lack of accurately parameterized diverse functional groups. This lack of diverse functional groups has severely limited the use of MM3 in pharmaceutical applications. 

Computational mechanics, and in particular the DE method, may be successfully used to analyze a wide range of operations involving powders and granular materials. Of particular relevance in a pharmaceutical context are applications related to flow of powders in hoppers (66), fluidized beds (67), and mixers (68,69). The method has been applied in the analysis of ball mills (70) and may be used to look more deeply into certain processes such as vibration-induced size segregation of granular materials (71) and packing (72). 

These successes did not go unnoticed by industry. Several pharmaceutical companies (1963-1964) became interested in applications of it-electron theory to biochemistry. While it was admittedly premature, it was felt that quantum chemistry was both the wave of the future and the very matrix for rational drug design. Hiickel energies of cephalosporins could be correlated with their biological activities.While companies were applying some mathematical methods of correlation techniques in quantitative structure-activity relationships (QSAR), it was chiefly the Hiickel theory and various forms of semiempirical quantum mechanics that was using a large share of computer time on the IBM 7094 mainframe in 1966. 

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