*4.4. Calculating Structure Features*

Secondary structure assignment was performed by DSSP [58], using a three-state classification distinguishing helical ('H','G','I'), extended ('B','E'), and irregular ('S','T', unassigned) residues.

Molecular surfaces were calculated using Naccess [59]. Solvent accessible surface area (SASA) was defined by the Nacces absolute surface column. Interface is defined as the increase in SASA as a result of removing interaction partners from the structure. Buried surface was calculated by subtracting interface area and SASA from the sum of standard surfaces of residues in the protein chain. Thus, interface and buried surfaces represent the area that is made inaccessible to the solvent by the partner(s) or by the analyzed protein itself. All calculated areas were split into hydrophobic (H) and polar (P) contributions based on the polarity of the corresponding atom. Polar/hydrophobic assignations were taken from Naccess.

Contacts were defined at the atomic level. Two atoms were considered to be in contact if their distance is shorter than the sum of the two atoms' van der Waals radii plus 1 Angstrom. For exact structural feature values for all MSF entries, see Supplementary Table S1.
