CINF 78 |
| Chemical-feature based pharmacophore models have been established as a state-of-the-art technique for characterizing the interaction between a macromolecule and a ligand [1]. While in ligand-based drug design, feature-based pharmacophore creation from a set of bio-active molecules is a frequently chosen approach, structure-based 3D pharmacophores are still lacking the reputation to be an alternative or at least a supplement to docking techniques. Nevertheless, 3D pharmacophore screening bears the advantage of being faster than docking and to transparently provide the user with all the information that is used by the screening algorithms to characterize the ligand-macromolecule interaction. Besides the presentation of our structure-based pharmacophore elucidation, our fast, rigid 3D pharmacophore superpositioning technique is applied to several examples. Geometric fitting of multi-conformational models of small organic molecules to structure-based pharmacophores is compared with docking methods and discussed in terms of conformational coverage, flexibility and eligibility for virtual screening. [1] H. Kubinyi. In Search for New Leads, EFMC - Yearbook 2003, pp. 14-28. |
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Herman Skolnik Award Symposium
2:00 PM-5:50 PM, Tuesday, 12 September 2006 Moscone Center -- Room 122, Oral
Division of Chemical Information |