Aspects of Molecular Modeling

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285 

It is helpful to begin by considering what constitutes molecular modeling. Although once interpreted by a few theoretical chemists as a derisive synonym for amateurish, watered-down, or incidental computational chemistry, the term is today quite respectable. In the pharmaceutical and chemical industries, the term molecular modeling is strongly associated with and used interchangeably with the term computational chemistry.  

The interpretation and ideas that the chemist gets from viewing a structure will depend on the quality of the computations that led to that representation. This point underscores the importance of understanding the concepts and limitations of the calculations that produced a particular model. For molecular mechanics energy minimizations or for molecular simulations, the quality of the force field and other parameters controlling the calculations underlies the quality of the computed results. In any approach to obtaining three-dimensional molecular structures, the quality of the model should be paramount in the mind of the user. 

We will discuss several approaches to obtaining realistic structures  

There are innumerable reviews and books on quantum mechanics that treat this subject from a detailed theoretical perspective. ° The level of treatment here is more elementary. The emphasis is on introducing concepts in a simple way and explaining some of the more commonly encountered terminology. A full mathematical development of quantum mechanical theory is beyond the scope of this forum. A how to approach to quantum mechanics is given in the excellent book by Clark. Other books may also be of interest to the reader. 

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Programming these constraints will require the same type of approach to the hydrogen bond aspect of molecular modeling as is already being applied to the molecular mechanics of covalent bonding. 

A general overview of the molecular modeling techniques applied to chiral hosts can be found in papers by Lipkowitz (77,78). Some special aspects of molecular modeling techniques related to chiral CE and earlier studies on the subject are summarized in Refs. 3, 17, 79, and 80. 

D. B. Boyd, Drug Inf. J., 17,121 (1983). Quantum Mechanics in Drug Design Methods and Applications. D. B. Boyd, D. W. Smith, J. J. P. Stewart, and E, Wimmer, J. Comput. Chem., 9, 387 (1988). Numerical Sensitivity of Trajectories across Conformational Energy Hypersurfaces from Geometry Optimized Molecular Orbital Calculations AMI, MNDO and MNDO/3. D. B. Boyd, in Reviews in Computational Chemistry, Vol. 1, K. B. Lipkowitz and D. B. Boyd, Eds., VCH Publishers, New York, 1990, pp. 321-354. Aspects of Molecular Modeling. 

Boyd, B. 1990. Aspects of Molecular Modeling. In Lipkowitz, K.B. and Boyd, D.B. (eds.), Reviews in Computational Chemistry. New York John Wiley Sons. 

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