Conformational Freedom in 3-D Databases

Abstract

With the advent of databases capable of storing full 3-D information on chemical structures, it is now feasible to search such databases for particular arrangements of atoms or functional groups. This is of particular importance in drug design, where known 3-D dispositions of atoms or groups (pharmacophores) are believed to be responsible for the physiological action of the drug. When designing a 3-D database system, it is necessary to include information on the conformational flexibility of a molecule, since a given molecule can exist in a variety of different conformations. This paper presents a novel way of storing this information, in which disk storage requirements and search times are independent of the number of conformations stored. A system based on this approach thus enables a true search to be performed, finding all possible matches to a given pharmacophore, not just those corresponding to the particular conformation stored. This paper describes the architecture of such a system and the processes that are carried out during a search, with special emphasis on the 3-D keys used to store and retrieve data.