Database Bioster

Schuffenhauer A, Gillet VJ, Willett P. Similarity searching in files of 3D chemical structures analysis of the BIOSTER database using 2D fingerprints and molecular field descriptors. J Chem Inf Comput Sci 2000 40 295-307. 

Chem. Inf. Comput. Sci., 43, 391-405. Schuffenhauer, A., Gillet, V.J. and Willett, P. (2000) Similarity searching in flies of three-dimensional chemical structures analysis of the BIOSTER database using two-dimensional flngerprints and molecular fleld descriptors. /. Chem. Inf. Comput. Sci., 40, 295-307. 

The retrieval of all 3D structures from a database considered to be similar to a given target structure is comparable with 2D similarity searching. 3D similarity searching raises the problem of conformational flexibility. Schuffenhauer et analysed the BIOSTER database by similarity search using 2D fingerprints and molecular field descriptors. A comprehensive overview on pharmacophore perception and 3D database searches is given in references 101 and 102. 

This section describes the application of Bioster database to medicinal chemistry problems. In the first example, the database was helpful in finding replacements for the pharmacologically unfavorable benzodioxole ring. Next, an earlier analysis is updated by tabulated examples of phenol bioisosteres. Finally, selected examples from a fragment query for a-ketoamide bioisosteres are presented. 

Here we briefly review the publications that have used the Bioster database as a source of bioisosteric fragments for the evaluation of bioisosteric (dis) similarity. 

An exhaustive analysis of 2995 molecule pairs extracted from the 98.1 version of Bioster database indicated that similarity measures based on 2D molecular fingerprints or electrostatic field descriptors were complementary although 2D methods could be adequate for similarity analyses [55]. To evaluate a range of similarity measures among synthetic substances and natural products, the Willett group also used 5024 compounds from Bioster database as well as sets of selected bioactive compounds from the more populous Chemical Abstract Service, ID-Alert, MACCS Drug Data Report, and NCI AIDS databases [56]. 

The applicability of LINGO, a text-based molecular representation derived from SMILES strings, to the discrimination of compounds with similar structure and activity was successfully tested on 7161 analogous molecule pairs extracted from the Bioster database and on the same number of random pairs [59, 60]. 

Schuffenhauer et al. [21] reported a comparative study ofbioisosteric replacements with UNITY 2D fingerprints and FBSS (field-based similarity search) using the Bioster database [22] as a source ofbioisosteric pairs. The authors report that both these 2D and 3D methods provide complementary results that were demonstrated to work synergistically when combined using data fusion. The UNITY fingerprint was reported to be very sensitive to heteroatom replacement. This sensitivity can be overcome somewhat by abstracting the atoms present in a structure into pharmacophoric features. 

The application of this topological fingerprint to a database of more than 700 000 structural fragments resulted in more than 2200 experimentally observed bioisos-teric R-groups, cores, and linkers from the Bioster database [22]. The descriptor was also optimized to increase the separation between experimentally observed bioisos-teric pairs and pairs selected at random. 

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