Binding thermodynamics discriminates fragments from druglike compounds: a thermodynamic description of fragment-based drug discovery - PubMed (original) (raw)
Review
. 2017 Apr;22(4):681-689.
doi: 10.1016/j.drudis.2016.11.019. Epub 2016 Dec 1.
Affiliations
- PMID: 27916639
- DOI: 10.1016/j.drudis.2016.11.019
Review
Binding thermodynamics discriminates fragments from druglike compounds: a thermodynamic description of fragment-based drug discovery
Glyn Williams et al. Drug Discov Today. 2017 Apr.
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.
Copyright © 2016 Elsevier Ltd. All rights reserved.
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