SHAPES library

Fig. 18.7 Molecular structures used in the SHAPES library. (A) Common drug frameworks used in the SHAPES library. The numbers denote the frequency of occurrence of each framework, and lone pairs indicate points of side-chain attachment...

X represents a C, N, O or S atom. (B) Common drug side chains used in the SHAPES library. The left-most atom indicates the point of attachment to the framework. Reproduced from Peng, et al. 2001 [1], 2001 Academic Press. 

Figure 12.34. Examples of molecular frameworks from the SHAPES library.

Finite element library subroutines containing shape functions and their derivatives in terms of local coordinates. 

This information will sufficiently define the function so that a design can be started. It defines the environment, sets the load level and the type of loading situation, and gives some idea of the shape requirements, as well as the possible aesthetics of the unit. It still permits a wide range of design choices as to material, structure, and shape but they would be limited to those normally used in a library environment. The more accurately and completely the function is defined, the more restricted are the design possibilities and the more detailed the specifications for the function. 

Andrews KM, Cramer RD. Toward general methods of targeted library design topomer shape similarity searching with diverse structures as queries. / Med Chem 2000 43 1723-40. 

Several extensions of wavelets have been developed to improve their ability to solve practical problems. Wavelet packets (Coifman and Wick-erhauser, 1992) are a library of basis functions that cover a wide variety of shapes. The library can be searched efficiently to select the best set of... 

Additional software has been developed to merge data from various data collection steps and to model the data using suitable statistical distribution functions. We are working on software to perform corrections for absorption, specimen shape, and misalignment. Library routines for 2-diraensional data smoothing and integration are being adapted to the calculation of orientation functions and other moments of the probability distributions. 

Another group has evaluated self-organizing maps [63] and shape/ pharmacophore models [64]. They developed a new method termed SQUIRREL to compare molecules in terms of both shape and pharmacophore points. Thus from a commercial library of 199,272 compounds, 1926 were selected based on self-organizing maps trained on peroxisome proliferator-activated receptor a (PPARa) "activity islands." The compounds were further evaluated with SQUIRREL and 7 out of 21 molecules selected were found to be active in PPARa. Furthermore, a new virtual screening technique (PhAST) was developed based on representation of molecules as text strings that describe their pharmacophores [65]. 

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