caa a22 4500 467938679 CHVBK 20180406153005.0 cr unu---uuuuu 170328e20060601xx s 000 0 eng 10.1007/s10822-006-9072-0 doi (NATIONALLICENCE)springer-10.1007/s10822-006-9072-0 Identification of target-specific bioisosteric fragments from ligand-protein crystallographic data [Elektronische Daten] [Elizabeth Kennewell, Peter Willett, Pierre Ducrot, Claude Luttmann] Bioisosteres are functional groups or atoms that are structurally different but that can form similar intermolecular interactions. Potential bioisosteres were identified here from analysing the X-ray crystallographic structures for sets of different ligands complexed with a fixed protein. The protein was used to align the ligands with each other, and then pairs of ligands compared to identify substructural features with high volume overlap that occurred in approximately the same region of geometric space. The resulting pairs of substructural features can suggest potential bioisosteric replacements for use in lead-optimisation studies. Experiments with 12 sets of ligand-protein complexes from the Protein Data Bank demonstrate the effectiveness of the procedure. Springer Science+Business Media, LLC, 2006 Bioisostere nationallicence Fragment substructure nationallicence Ligand-protein complex nationallicence Protein Data Bank nationallicence Shape similarity nationallicence Kennewell Elizabeth Krebs Institute of Biomolecular Research and Department of Information Studies, University of Sheffield, S1 4DP, Sheffield, UK aut Willett Peter Krebs Institute of Biomolecular Research and Department of Information Studies, University of Sheffield, S1 4DP, Sheffield, UK aut Ducrot Pierre Chemical Sciences, Sanofi-Aventis, 94400, Vitry-sur-Seine, France aut Luttmann Claude Chemical Sciences, Sanofi-Aventis, 94400, Vitry-sur-Seine, France aut Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/6(2006-06-01), 385-394 0920-654X 20:6<385 2006 20 10822 https://doi.org/10.1007/s10822-006-9072-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10822-006-9072-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kennewell Elizabeth Krebs Institute of Biomolecular Research and Department of Information Studies, University of Sheffield, S1 4DP, Sheffield, UK aut NATIONALLICENCE 700 1- Willett Peter Krebs Institute of Biomolecular Research and Department of Information Studies, University of Sheffield, S1 4DP, Sheffield, UK aut NATIONALLICENCE 700 1- Ducrot Pierre Chemical Sciences, Sanofi-Aventis, 94400, Vitry-sur-Seine, France aut NATIONALLICENCE 700 1- Luttmann Claude Chemical Sciences, Sanofi-Aventis, 94400, Vitry-sur-Seine, France aut NATIONALLICENCE 773 0- Journal of Computer-Aided Molecular Design Kluwer Academic Publishers 20/6(2006-06-01), 385-394 0920-654X 20:6<385 2006 20 10822 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer