Fig. 9

Water-mediated H-bonds were observed during the MD simulations of a TTR-resveratrol structure. a, b The lower-resolution crystal structure (1DVS) contains two water molecules within the binding site. One forms a water-mediated H-bond to Glu54A. c, d During MD simulations, an extensive water-mediated H-bond network was formed within the binding site, including residues from chains A and C. A frame from a 930\(^{th}\) ns is chosen for visualization. e Bridge2 output of the resveratrol water-mediated H-bonding. Values on the edges represent the average number of bridging water molecules during the main MD simulation of the low resolution structure. Corresponding figures from remaining simulations are deposited in Supporting Information Fig. S11i-k. Blue cartoons represent the backbone of H-bonding amino-acid residues, and sticks with grey carbons their side-chains. Resveratrol (STL) is presented by sticks of green carbons, and waters by balls-and-sticks representation (red oxygens, white hydrogens). Direct H-bonds are shown with purple dotted lines, and water mediated ones with cyan dotted lines. f 7Q9O in yellow-colored cartoon model with green stick model ligand is overlaid with 2fo-fc electron density map in light-blue mesh. Crystal-modelled waters that were fitted to the electron density are emphasized by dark-blue spheres. Our MD snapshot is superposed (rose-colored cartoon model with light-pink stick model ligand) with MD TIP3 waters of the inspected snapshot in element-colored stick model (red oxygen and white hydrogens). It can clearly be observed that all modelled crystal water locations are also occupied by MD TIP3 waters