Searches, in 3D databases

This method represents the most common and traditional application of computational tools to rational drug design. From a list of molecules of known activity, one can establish a 3D-pharmacophore hypothesis that is then transformed into a 3D-search query. This query is then used to search a 3D database for structures that fit the hypothesis within a certain tolerance. If the yield of active molecules is significant, then the query can be used to predict activities on novel compounds. In our situation, the enantiophore is built from the superposition of a list of sample molecules, which are all well separated on a given CSR Hence, the common features of this series of molecules can become a good enantiophore hypothesis for the enantiores-olution on this CSR... 

Giiner, O. F. and Henry, D. R. Formula for determining the goodness of hit lists in 3D database searches. At URL http //www.netsci.orp/Science/Cheminform/ feature09.html. 

Sadowski, J. (1997) A hybrid approach for addressing ring flexibility in 3D database searching. J Comput Aided Mol Des 11, 53-60. 

Many different structural descriptors have been developed for similarity searching in chemical databases [4] including 2D fragment based descriptors, 3D descriptors, and descriptors that are based on the physical properties of molecules. More recently, attention has focused on diversity studies and many of the descriptors applied in similarity searching are now being applied in diversity studies. Structural descriptors are basically numerical representations of structures that allow pairwise (dis)similarities between structures to be measured through the use of similarity coefficients. Many diversity metrics have been devised that are based on calculating structural (dis)similarities, some of these are described below. 

By using the 3D arrangement of atoms in a molecule and the calculated physicochemical properties of these atoms, it is possible to calculate molecular descriptors. Since the descriptor is typically a mathematical vector of a fixed length, we can use it for a fast search in a database, provided that the database contains the equivalent descriptor for each data set and that the descriptor is calculated for the query. We have seen before that particularly similarity and diversity can be excellently expressed with molecular descriptors. 

Role of 3D-QSAR in 3D Database Searching, Combinatorial Library Design, and Computer De Novo Design... 

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