title: Binding thermodynamics discriminates fragments from druglike compounds: a thermodynamic description of fragment-based drug discovery.
abstract: Small is beautiful - reducing the size and complexity of chemical starting points for drug design allows better sampling of chemical space, reveals the most energetically important interactions within protein-binding sites and can lead to improvements in the physicochemical properties of the final drug. The impact of fragment-based drug discovery (FBDD) on recent drug discovery projects and our improved knowledge of the structural and thermodynamic details of ligand binding has prompted us to explore the relationships between ligand-binding thermodynamics and FBDD. Information on binding thermodynamics can give insights into the contributions to protein-ligand interactions and could therefore be used to prioritise compounds with a high degree of specificity in forming key interactions.
authors.affiliation: Astex Pharmaceuticals, 436 Cambridge Science Park, Milton Road, Cambridge CB4 0QA, UK.
authors.forename: Glyn
authors.initials: G
authors.lastname: Williams
authors.affiliation: Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok krt. 2, H-1117 Budapest, Hungary.
authors.forename: György G
authors.initials: GG
authors.lastname: Ferenczy
authors.affiliation: CVMD Innovative Medicines, AstraZeneca R&D Mölndal, S-43183 Mölndal, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Ulander
authors.affiliation: Medicinal Chemistry Research Group, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Magyar tudósok krt. 2, H-1117 Budapest, Hungary. Electronic address: gy.keseru@ttk.mta.hu.
authors.forename: György M
authors.initials: GM
authors.lastname: Keserű
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry*; D054852:Small Molecule Libraries / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D008024:Ligands; D011506:Proteins; D054852:Small Molecule Libraries