DISCO program

In a recent review the pharmacophore identification programs Catalyst, DISCO, and GASP have been compared [83]. 

Muscarinic M3 Receptor. A pharmacophore model was derived from known M3 receptor antagonists, using the program DISCO, and 3D searching was performed by Unity 3D in the Astra Charnwood in-house compound repository and the databases of several commercial suppliers. The 172 compounds that fitted the pharmacophore were screened for their M3-antagonistic potency. Several compounds with micromolar and even submicromolar activities resulted, for example, compound 13 (A50 M3 antagonism 0.2pM pA2 = 6.67 Fig. 16.2) [85],... 

Even though the original authors of DISCO do not consider it to be an automated pharmacophore identification program [53], we decided to include the method in this review because of its considerable influence over the development of modern pharmacophore modeling tools. 

By design, no conformational engine was implemented in DISCO, based on the assumption that at the time, no universal force fields and methods suitable for all types of compounds were available [53]. However, the commercial distributor Tripos provides access to 3D converters and conformational search engines such as Concord and Confort via the Sybyl interface. These algorithms will not be reviewed here as strictly seen they are not part of any pharmacophore identification program. The distance geometry approach has been used... 

Do I like the proposed hypothesis Although very subjective, this approach tends to counter-balance the inherent imperfections of automated methods. Programs such as DISCO and HipHop will provide multiple output models among which the expert has to choose the most acceptable. The eye is often the first and best critic for the pharmacophore hypotheses. 

ALADDIN (91). DISCO uses a rapid technique, clique detection, to identify maps from the set of all potential pharmacophore points. Typically, the maps are generated in a few minutes of CPU time and the results can be viewed in a variety of molecular modeling programs. 

The Bron-Kerbosh clique detection is used iteratively to find sets of common distances, i.e., cliques, obtaining thereby disco solutions, e.g., pharmacophore maps chirality is also considered by evaluating the sign of the torsion angle for quadruplets of non-coplanar points. In family only one pair of structures is composed at a time for grouping structures into families. The program compair makes similar pairwise comparisons employing a user-supplied reference structure each time. 

Patel, Y., Gillet, V. J., Bravi, G., Leach, A. A comparison of the pharmacophore identification programs Catalyst, DISCO and GASP. J. Comput.-Aided Mol. Des. 2002,16,653-681. 

Finally, the discussion of 3D MCS algorithms is closely related to the emerging technique of pharmacophore mapping, which seeks to provide automated tools for the identification and subsequent representation of pharmacophore models for sets of biologically related compounds, that is, the 3D chemical and spatial requirements for bioactivity (as reviewed by Bures et al.). 2 An example of work in this area is the DISCO (Distance Comparisons) program that has been developed by Martin et al.203 DISCO identifies the maximum overlap (to within allowed interatomic distance tolerances) between a set of structures, which can be either a set of different molecules or a set different... 

Y. C. Martin, M. G. Bures, E. A. Danaher, J. DeLazzer, I. Lico, and P. A. Pavlik, J. Comput.-Aided Mol. Design, 7, 83 (1993). A East New Approach to Pharmacophore Mapping and Its Application to Dopaminergic and Benzodiazepine Agonists. (The program known as DISCO is distributed by Tripos Associates, St. Louis, MO.)... 

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