FIGURE 1.

Ribbon structures of fibrin(ogen) (A), the A:a knob-hole bond (B and C), and the B:b knob-hole bond (D and E). The structures correspond to the A:a knob-hole complex (model system Aa1) and B:b knob-hole complex (system Bb1), respectively, at pH 7 and T = 25 °C. B and D, the interface of the A:a knob-hole complex (B) and B:b knob-hole complex (D) in which the binding determinants, loop I (region I shown in blue), interior region (region II shown in green), and moveable flap (region III shown in red), interact with peptides GPRP and GHRP (shown in orange), respectively. C and E, simulation setup. Holes ‘a’ and ‘b’ are constrained through fixing the C termini of the γ chain (residue γGly¹⁶⁰) and β chain (residue βVal²⁰⁵), respectively (see “Experimental Procedures”). A constant pulling force f (represented by the black arrow) is applied to the Pro⁴ residue of GPRP peptide and Pro⁴ residue of GHRP peptide in the direction perpendicular to the binding interface to dissociate the knob-hole bond. Also shown are structural details of A:a and B:b knob-hole bonds in which residues in binding regions I–III in holes ‘a’ and ‘b’ establish binding contacts with peptides GPRP and GHRP.