Fig. 4.

Analysis of relative escape times associated with mutating the binding residues of known HmAbs identifies potential difficult to escape HmAbs. a Minimum escape time across all residues $t_e^{min}$ (top panel) and number of residues with relatively short escape times $n_e^{\tau }$ (bottom panel) in the binding residues of 16 HmAbs, determined using global alanine scanning³⁸. The binding residues of the HmAbs are defined as the mutations that resulted in reduction of binding with respect to the wild-type to ≤ 20%. HmAbs are colored according to the antigenic domains using the scheme in Fig. 3b. The background of the HmAbs predicted to be relatively escape-resistant ($t_e^{min}>\zeta$) is shaded. b Location of binding residues of four HmAbs identified as relatively escape-resistant are shown as spheres on the available crystal structure (PDB ID 4MWF⁴³). Heat map shows the escape times ($t_e^i$) associated with incurring mutations at antibody-binding residues similar to Fig. 3