Table 1. Summary of all interactions defined in RIP-MD.

Cα contacts	dist (Cαi, Cαj) ≤ d	d = 8 Å
Hydrogen bonds	dist (donor, acceptor) ≤ d $\text{θ}(\overrightarrow{C-H},\overrightarrow{\text{acceptor}})\ge a$	d = 3 Åa = 120°
Salt bridges	Contacts between NH/NZ groups of ARG/LYS and OE*/OD* in ASP/GLU ≤ d	d ≤ 6 Å
Disulfide bonds	S atoms of two cysteins ≤ d dihedral θ(C − S − S − C) ∈ [a, b]	d ≤ 3 Åa ≥ 60° and b ≤ 90°
Cation-π interactions*	Distance between aromatic rings ≤ d	d ≤ 6 Å
π–π interactions*	dist (aromatic ring, cation) ≤ d$\text{θ\hspace{0.17em}}(\overrightarrow{\text{normal vector ring}},\overrightarrow{\text{ring center}-\text{cation}})=a$	d = 7 Åa ∈ [0°, 60°] or a ∈ [120°, 180°]
Arg–Arg	dist (guanidine1, guanidine2) ≤ d	d ≤ 5 Å
Coulomb interactions	Charged-group based cut-off using a 1–4 potential
van der Waals	12-6 Lennard–Jones potential

Notes:

A detailed description can be found in Text S1.

^*His residues are considered as a cation if they present a protonated nitrogen atom, and as π-system only if they are not protonated. Other π-systems considered are the aromatic rings of Phe, Tyr, and Trp.