Fig. 3: Molecular dynamics (MD) simulations show that binding of Fab15H6.v4 to LoopA locks HTRA1 in a non-competent state.

a Detailed conformational differences within the catalytic center of competent (brown, pdb 3TJN_chainB) and Fab-bound HTRA1^PD (blue). The distance (dashed line) between L345 and S328 decreases from competent (green) to the non-competent conformation (red) where it occludes the S1 pocket. The distance (dashed line) between H220 and S328 increases when transitioning from the active (green) to the inactive (red) conformation, impeding the hydrogen transfer during catalysis. b, c Measured distance between L345^Cγ1 and S328^Oγ (b) and between H220^Nε2 and S328^Oγ (c) during the MD simulations of competent HTRA1^PD (wheat) with the calculated distances of competent and non-competent conformation indicated by green and red dotted lines, respectively. d, e Measured distance between L345^Cγ1 and S328^Oγ (d) and between H220^Nε2 and S328^Oγ (e) during the MD simulations of Fab-bound HTRA1^PD (blue). Expected distances for competent and non-competent conformations are indicated by green and red dotted lines, respectively. f Principal component analysis of MD simulations of 3TJN_chainB and the Fab-bound HTRA1^PD, showing cross plots of the first two individual principal components.