  Mucin glycoprotein consist of tandem repeating glycosylated regions flanked
by non-repetitive protein domains with little glycosylation. These
non-repetitive domains are involved in the pH dependent gelation of gastric
mucin, which is essential to protecting the stomach from autodigestion. We have
examined the folding of the non-repetitive sequence of von Willebrand factor
vWF-C1 domain (67 amino acids) and PGM 2X (242 amino acids) at neutral and low
pH using Discrete Molecular Dynamics. A four-bead protein model with hydrogen
bonding and amino acid-specific hydrophobic/hydrophilic and electrostatic
interactions of side chains) was used. The simulations reveal that the distant
N- and C-terminal regions form salt-bridges at neutral pH giving a relatively
compact folded structure. At low pH, the salt bridges break giving a more open
and extended structure. The calculated average value of the beta-strand
increases from 0.23 at neutral pH to 0.36 at low pH in very good agreement with
CD data. Simulations of vWF C1 show 4-6 beta strands separated by turns/loops
and we found that pH did not affect significantly the folded structure. The
average beta-strand structure of 0.32 was again in very good agreement with the
CD results.
