Figure 4.

Evidence for structural water molecule in eptinezumab:CGRP interface. CGRP is colored in yellow and CDR L2 in Limon, using PyMOL color names. The locations of water molecules from the X-ray crystallography structure of the uncomplexed eptinezumab (orange spheres), of water molecules obtained by Watermap from the complex structure (light blue spheres 1–3), and of explicit clusters of water molecules obtained by Watermap from the eptinezumab:CGRP complex (HOH clusters). Watermap places 2 water molecules (light blue spheres 1 and 2) in a cavity within the bound structure, forming a network of hydrogen bond between Asp51 NH (CDR L2) to water1, water1 to water2, water2 to Leu90 C = O and Ser92 OG (CDR L3), and finally Ser92 OGH to Ser116 C = O (CGRP); CGRP Ser116 OGH does not make any direct interaction with eptinezumab but faces another small cavity. Watermap placed one water molecule (light blue sphere 3) in this cavity, indicating a hydrogen bond network with O from water3 and water3 to Cys100 and Tyr93 (CDR L3) carbonyls