Metastable conformational states of the phosphodiesterase 5 (PDE5) enzyme are shown in the apo state (leftmost panels) and two inhibitor-bound states, the allosteric inhibitor evodiamine-bound PDE5 (middle panels), and the competitive inhibitor avanafil-bound PDE5 (rightmost panels). The conformational states correspond to minima in the free energy surfaces (top panels) labeled with blue, orange, and red dots. For details, see: Shubhandra Tripathi et al., Protein Science, 2023. https://doi.org/10.1002/pro.4720