| Search Techniques for Rational Drug Design (2007) | |||||||||||||||
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| Pharmaceutical drug design is a long and expensive process. Early selection of promising molecules can dramatically improve this process, but this selection is often similar to searching for a needle in a haystack. In most cases, all what a chemist initially has is a small collection of molecules that exhibit enough desired activity to hypothesize that they share a 3-D atomic substructure binding to the same receptor site. A key problem is to identify this substructure, which can then be used as a pattern to screen databases of molecules. This problem is complicated by the fact that a drug molecule is "flexible" and can achieve many low-energy (stable) states. In this paper we present search techniques that we have developed to find these low-energy states and to identify common 3-D substructures that appear in at least one low-energy state of most molecules in a given collection. We also show experimental results obtained with a software system implementing these techniques. 1 Introd... | |||||||||||||||
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