title: Applying thermodynamic profiling in lead finding and optimization.
abstract: Small-molecule drug discovery involves the optimization of various physicochemical properties of a ligand, particularly its binding affinity for its target receptor (or receptors). In recent years, there has been growing interest in using thermodynamic profiling of ligand-receptor interactions in order to select and optimize those ligands that might be most likely to become drug candidates with desirable physicochemical properties. The thermodynamics of binding is influenced by multiple factors, including hydrogen bonding and hydrophobic interactions, desolvation, residual mobility, dynamics and the local water structure. This article discusses key issues in understanding the effects of these factors and applying this knowledge in drug discovery.
authors.affiliation: Institute of Pharmaceutical Chemistry, University of Marburg, Marbacher Weg 6, D35032 Marburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Klebe
mesh_terms: D001665:Binding Sites; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D055808:Drug Discovery / Q000379:methods*; D006860:Hydrogen Bonding; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology; D013816:Thermodynamics
chemical_list: D008024:Ligands; D054852:Small Molecule Libraries