Text S1_final

Rosetta energy terms used in energy calculations The contribution towards fold stability (ERESFold) of each mutated residue i at each sequence position j was estimated by recording the sum of interand intra-residue Rosetta energy terms: ERESFold, i,j = E_LJatr (i,j) + E_LJrep (i,j) + G_sol (i,j) + E_dun (i,j) + E_hb (i,j) + E_prob (i,j) + E_pair (i,j) – E_ref (i,j), where: E_LJatr: attractive component of Rosetta Lennard-Jones potential E_LJrep: repulsive component of Rosetta Lennard-Jones potential G_sol: Rosetta implicit solvation term E_dun: Rosetta rotamer probability term E_hb: Rosetta hydrogen bonding term E_prob: Rosetta probability of amino acid type, given the backbone conformation E_pair: Rosetta pair term E_ref: Rosetta reference energy The contribution of each mutated residue to stability of the dimer interface (ERESDimer) was estimated by calculating only inter-chain pair-wise Rosetta energy function contributions between the mutated residue and neighboring residues on the opposite dimer chain (each interface term was calculated only over sets of residues where chain(residue 1) != chain (residue2)): ERESDimer (i,j) = E_LJatr_interface (i,j) + E_LJrep_interface (i,j) + G_sol_interface (i,j) + E_hb_interface (i,j) + E_pair_interface (i,j)