The fibrin central E region contains two sets of polymeric knobs A and B, which are hidden in fibrinogen but are exposed after thrombin cleavage of fibrinopeptide A (FpA) and fibrinopeptide B (FpB) from the N-terminus of the Aα- and Bβ-chains, respectively. The location of the binding holes and possible models for knob-hole interactions can be known by X-ray crystallographic studies using synthetic peptide analogs of knobs A and B. When fibrinogen fragment D and dual D are crystallized in the presence of two peptide analogs, the knob A peptide mimic H-Gly-Pro-Arg-Pro-NH2 (GPRP-amide) interacts with residues γ364Asp, γ330Asp, γ329Gln, and γ340His found in hole a to form H bonds, the knob B peptide mimic H-Gly-His-Arg-Pro-NH2 (GHRP-amide) interacts with Bβ397Glu, Bβ398Asp, and Bβ432Asp in hole b.