Drug–Target Association Kinetics in Drug Discovery Adriaan P. IJzerman, Dong Guo  Trends in Biochemical Sciences  DOI: 10.1016/j.tibs.2019.04.004 Copyright © 2019 Elsevier Ltd Terms and Conditions

Figure 1 Kinetics Map across Several Drug Targets, Where a Compound’s Affinity (KD, Parallel Diagonal Lines) Was Resolved into Its koff (x Axis) and kon (y Axis) Values. Trends in Biochemical Sciences DOI: (10.1016/j.tibs.2019.04.004) Copyright © 2019 Elsevier Ltd Terms and Conditions

Figure 2 Schematic Representation of Ligand Association to a Given G Protein-Coupled Receptor (Green Lines). The ligand (orange spheres) makes an initial contact with the extracellular surface (light grey box) of the receptor at the so-called extracellular vestibule to form a metastable intermediate conformation. Substantial desolvation (water molecules, blue spheres) takes place at this step, representing a major energetic barrier to binding. Afterwards, the ligand enters into the orthosteric binding site (dark grey box) with a relatively fast speed. Trends in Biochemical Sciences DOI: (10.1016/j.tibs.2019.04.004) Copyright © 2019 Elsevier Ltd Terms and Conditions

Figure I Schematic Representation of Ligand–Receptor Binding Models, Exemplified for the Case of G Protein-Coupled Receptors. Trends in Biochemical Sciences DOI: (10.1016/j.tibs.2019.04.004) Copyright © 2019 Elsevier Ltd Terms and Conditions