File Name : figs1.tiff

Caption : figure s1:simulated system—this is also fig.  1 in the main text and is reported here for convenience.  in fig.  s1, theζcoordinate is defined as in panel c).  in figs s2 and s3,the color scheme of the residues which aids reading the hydrogen bond network is retained from panel a)

File Name : figs2.tiff

Caption : figure s2:relative stability between the trans- and cis-pro32—relative stability(in kj/mol) of the isomers during the metadynamics simulations. the white window accounts for the equilibration time, so it is discarded for the integration. the free energy profiles in fig.2 of the main text are obtained  by  integrating  the  free  energy  for  eachζpoint  of the curve. the time window for the integration is reported in light blue. the integration procedure is described in ref. 52 of the main text.

File Name : figs3.tiff

Caption : figure s3:normalized hydrogen bond occurrence for each residue and each con-formation during the metadynamics for the wild-type—the configurations of the proteins are clustered from the snapshots of the metadynamics by selecting theψandζco-ordinates. the selection window surrounds the minima of the maps reported in fig.2. the structures sampled correspond to the most probable structures of the protein when pro32 is in trans or cis. the color scheme refers to fig.s1

File Name : figs4.tiff

Caption : figure s4: normalized hydrogen bond occurrence for each residue and each con-formation during the metadynamics for d76n —the color scheme refers to figures1

File Name : figs5.tiff

Caption : figure s5:structure alignment of the residues surrounding cis and trans pro32—. starting from the most populated clusters of the free energy minima, we show the arrangement of the relevant residues to the h-bond network presented in table 2 and figure 3 of the main text, focussing on the surroundings of the pro32.