Fragment-based search

Two approaches have been published recently which combine rapid fragment-based searching techniques with sophisticated MD or MC simulations. 

GROUPBUILD [68] fragment-based, sequential growth, combinatorial search ... 

SKELGEN [78] smaU-fragment based, Monte-Carlo search ... 

Chen, X., Reynolds, . H. (2002) Performance of similarity measures in 2D fragment-based similarity searching comparison of... 

In the MOE environment, molecules are stored in a database with their associated set of conformations. Several methods can be applied to expand the conformational space of organic molecules ranging from molecular dynamics to stochastic methods and systematic search. A fragment-based high-throughput... 

In the second step, the lead is modified. This could be performed in some variants. The lead compound can be enlarged by individual atoms or by molecular fragments. Both approaches have several advantages and disadvantages.34 Building up a new molecule atom by atom can produce any possible structure, and thus a complete space of possible molecules is searched but, unfortunately, most of the obtained structures are not easily accessible by means of chemical synthesis. On the other hand, fragment based approach generates mainly structures which are... 

DEREK Searches for toxic fragments based on predefined rules Can be modified and extended to include new rules Structurally diverse chemicals Compounds are limited to 64 atoms Runs only on VAX machines under VMS Qualitative... 

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. 

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