title: Is there a link between selectivity and binding thermodynamics profiles?
abstract: Thermodynamics of ligand binding is influenced by the interplay between enthalpy and entropy contributions of the binding event. The impact of these binding free energy components, however, is not limited to the primary target only. Here, we investigate the relationship between binding thermodynamics and selectivity profiles by combining publicly available data from broad off-target assay profiling and the corresponding thermodynamics measurements. Our analysis indicates that compounds binding their primary targets with higher entropy contributions tend to hit more off-targets compared with those ligands that demonstrated enthalpy-driven binding.
authors.affiliation: Discovery Chemistry, Gedeon Richter Plc, 19-21 Gyömrői út, H-1103 Budapest, Hungary.
authors.forename: Ákos
authors.initials: Á
authors.lastname: Tarcsay
authors.affiliation: Research Centre for Natural Sciences, Hungarian Academy of Sciences, 2 Magyar tudósok krt, H-1117 Budapest, Hungary. Electronic address: gy.keseru@ttk.mta.hu.
authors.forename: György M
authors.initials: GM
authors.lastname: Keserű
mesh_terms: D002626:Chemistry, Pharmaceutical; D008024:Ligands; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D013816:Thermodynamics
chemical_list: D008024:Ligands; D004364:Pharmaceutical Preparations