DISCOtech

Overview

In the absence of a receptor structure, the identification or optimization of a lead depends on discovering the pharmacophore?€”the shared molecular features and their spatial relationship essential for biological activity. Starting from a set of precomputed conformers for a set of ligands, DISCOtech™ uses clique detection¹ methods to generate multiple pharmacophore hypotheses that can be compared and refined.

Pharmacophore models serve as alignment rules in QSAR with CoMFA^® for lead optimization and as queries for a UNITY^® 3D flexible database search to identify potential lead compounds.

DISCOtech Brochure (614k)

Angiotensin II receptor antagonists and their pharmacophore determined by DISCOtech. The model is displayed as a UNITY query using lines to represent interfeature distances and spheres color-coded by type to represent features. Atoms that hit the UNITY query based on the model are shown in yellow.

Key Benefits

• Streamlined, easy-to-use interface minimizes the need for user intervention while still allowing full control of parameters.
• Requires no advance knowledge of key functional groups or predefined correspondences between functional groups in different ligands.
• Donor/acceptor sites are represented as UNITY features, allowing DISCOtech models to be used directly in UNITY searches to locate compounds in databases that satisfy pharmacophore models.
• Novel tools that evaluate interfeature distances ensure diversity in the conformers selected for model generation.
• Clique detection algorithm produces the highest quality models possible by automatically iterating through the adjustable parameters (distance tolerance, number of features, and molecules used) until the default or user-specified limits are reached.
• Straightforward mechanism for model refinement enables easy selection of new input conformers based on similarity to a particular model.