3-D searching

Sheridan RP, Nilikantan R, Rusinko A, Bauman N, Haraki K, Venkataraghavan R, 3-D SEARCH A system for three-dimensional substructure searching, J. Chem. Inf. Comput. Sci., 29 255-260, 1989. 

Pearlman, R.S. (1993) 3D molecular structures generation and use in 3 D searching, in 3D QSAR in Drug Design. Theory, Methods and Applications (ed. H. Kubinyi), ESCOM, Leiden, The Netherlands, pp. 41-79. 

The simple, two-stage procedure described above characterizes many current 2-D substructure searching systems (15), and also forms the basis for the 3-D searching systems described later in this review that said, the reader should note that other approaches to 2-D substructure searching are possible (see, e.g., refs. 44-46). 

The effectiveness of any 3-D searching program will be maximized if it is closely integrated with a molecular modeling and graphics program. There... 

It will be clear from what has been said in this review that 3-D searching systems have developed with great rapidity since their introduction in the late 1980s and that they already provide a range of facilities that would have appeared quite remarkable only a few years ago. That said, there are still many areas where considerable research and development is needed if computational chemists are to be provided with appropriate tools to assist... 

The first operational system for searching a 3-D database of nontrivial size was reported in 1987 (78) since then, the field of 3-D searching has been extremely rapid growth, and there are already several documented examples of the utility of 3-D searching in real research programs, as discussed in Section IV. This progress has occurred because of the converging interests... 

If only the structure of the enzyme/receptor is known, energy calculations between functional group probes and the active site residues of the enzyme/ receptor can be used to determine favourable positions ( hot spots ) to place the functional group. These hot spots can readily be converted into a pharmacophore model for use in a 3-D search. 

Since 1986, others have developed their own speciaUsed 3-D searching systems. These systems include the ALADDIN system developed at Abbott, the 3DSEARCH system developed at Lederle, and the MACCS-3D system developed by Molecular Design Limited in collaboration with an industrial consortium. Any one of these systems can be used to develop synthetic targets using the strategy outlined above. 

The ACL shown in Figures 5 and 7 was used to transform the database structures into molecules to be synthesised. The ALADDIN search of a database of carefully modelled 3-D structures used in studies of a variety of medicinal chemistry projects identified 13016 potential compounds for synthesis. The MODSMI transformations reduced this number to 2529, an 80% reduction. Two slightly different searches of CONCORD structures of compounds in the Fine Chemicals Directory produced 12996 and 6559 original hits that were transformed into 1874 and 2247 unique compounds for an 85% and 66% reduction, respectively. Finally, the ALADDIN search of CONCORD structures of compounds in POMONA89 resulted in 10319 hits which were transformed into 2314 unique compounds for a 78% reduction in the number of compounds to be considered. Clearly the MODSMI transformations reduce the number of compounds to be handled by later steps. Thus this is a very useful strategy for evaluation of hits from a 3-D search. 

D SEARCHING AND NUMERICAL ANALYSES APPLIED TO FILES OF CRYSTALLOGRAPHIC DATA METHODOLOGIES, EXAMPLES, AND INTEGRATION WITH 1-D AND 2-D TECHNIQUES. 

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