3 – Molecular Modeling of Small Molecules

This chapter attempts to demonstrate that molecular modeling, in particular; and simulation, in general, represent complementary alternatives to theory and experiment for solving scientific problems. In attempts to predict the properties of new systems, experiment is expensive and often difficult, and needs direction to be productive. Also, theory is usually insufficient to get the prediction exactly right. In our experience, models—mathematical/statistical, molecular, and mechanistic—can harness theory and can indicate the correct experiments to run. Reasons for performing a modeling study are numerous. The best reasons are to understand an experimental system or results; to optimize information to be derived from a planned experiment; or to apply theoretical or structural information to a scientific problem. There are many possible methods and applications of molecular modeling. The chapter attempts to give the reader a feel for the types of studies that can be done, and why they would be done. Molecular structures may be generated by a variety of procedures. This chapter discusses structure generation or retrieval; structure visualization; conformation generation; deriving bioactive conformations; molecule superposition and alignment; deriving the pharmacophoric pattern; receptor mapping; estimating biological activities molecular interactions; docking; calculation of molecular properties; and energy calculations. Once a structure is created, a number of techniques may be used to generate different conformations of the structure and to rate them. One of the most popular uses of molecular modeling systems is to visualize molecular structures and interactions in order to calibrate the chemist's intuition.

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