The central E region of fibrin contains two sets of polymerization knobs, A and B, that are cryptic in fibrinogen but become 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 are known from X-ray crystallographic studies using synthetic peptide analogs of knobs A and B. When fibrinogen fragment D and double-D are crystallized in the presence of both peptide analogs, the knob A peptide mimic H-Gly-Pro-Arg-Pro-NH₂ (GPRP-amide) forms H-bond interactions with residues γ364Asp, γ330Asp, γ329Gln, and γ340His found in hole a. In the same manner, the knob B peptide mimic H-Gly-His-Arg-Pro-NH₂ (GHRP-amide) interacts with residues Bβ397Glu, Bβ398Asp, and Bβ432Asp in hole b.