(A) Correlation of CAP photo-isomerization kinetics (κ/I) and energetics (ΔEcis-trans). The values of κ/I ratio of ChemMatrix-bound CAPs are plotted against the normalized values of ΔEcis-trans derived in silico via MD modeling of the corresponding CAPs; the dotted line data are reported from prior work on CAPs39. (B) Structures of the complexes formed by human FVIII and the cis isomers of CAP.14mY and CAP.16mY; the cis-CAP isomers are in magenta, the A1 domain of human FVIII (PDB ID: 3CDZ) is in pink, while all other FVIII domains are in grey. (C) Values of rFVIII binding strength (dark red), elution efficiency (light red), and selectivity (blue diamonds) of sequence-based variants of CAP.14 and CAP.16 conjugated on ChemMatrix beads at different values of ionic strength of the mobile phase - namely X M NaCl (X: 0.1, 0.25, 0.5, 0.75, and 1) added to 0.1 M HEPES buffer, 5 mM CaCl2, and 0.01% v/v Tween20 at pH 7.4. The values of rFVIII binding strength, selectivity, and elution, and error bars were calculated as described in Figure 2.