Molecular modeling screening techniques

In the search for new drug candidates, scientists use molecular modeling techniques to identify potentially new structural moieties and screen natural sources or large families of synthetically related compounds, along with modifying exisiting compounds. Once a potentially new drug has been iden-... 

The quest for functionalized lead structures that effectively mimic the "hot spots" within the biological ligand is not easy (68). Molecular modeling and high-throughput screening (HTS) are techniques that are currently used for this purpose and have been summarized elsewhere. 

The above topological shape analysis techniques can replace visual shape comparisons of molecular models on the computer screen with precise, reliable, and reproducible numerical comparisons of topological shape codes. These comparisons and the similarity or complementarity rankings of molecular sequences can be performed by the computer automatically. This eliminates the subjective element of visual shape comparisons, a particularly important concern if large sequences (e.g. several thousands) of molecules are to be compared. In the data banks of most drug companies there is information stored on literally hundreds of thousands of molecules, and their detailed shape analysis by visual comparison on a computer screen is clearly not feasible. By contrast, automatic, numerical, topological shape analysis by computer is a viable alternative. 

The anxiolytic agents currently on the market owe much to serendipity as well as rational design in their genesis. With the exception of buspirone, all first indication anxiolytics were introduced before 1975, before many of the modern techniques of medicinal chemistry such as radioligand binding assays, molecular modeling, and pharmacokinetic screening were introduced into common practice. 

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