Background: Protein glycosylation, the covalent attachment of carbohyd
rates, is very common, but in many cases the biological function of gl
ycosylation is not well understood. Recently, fluorescence energy tran
sfer experiments have shown that glycosylation can strongly change the
global conformational distributions of peptides, We intend to show th
e physical mechanism behind this structural effect using a theoretical
model. Results: The framework of the hp model of Dill and coworkers i
s used to describe peptides and their glycosylated counterparts, Confo
rmations are completely enumerated and exact results are obtained for
the effect of glycosylation. On glycosylation, the model peptides expe
rience conformational changes similar to those seen in experiments. Th
is effect is highly specific for the sequence of amino acids and also
depends on the size of the glycan, Experimentally testable predictions
are made for related peptides. Conclusions: Glycans can, by means of
entropic contributions, modulate the free energy landscape of polypept
ides and thereby specifically stabilize polypeptide conformations. Wit
h respect to glycoproteins, the results suggest that the loss of chain
entropy during protein folding is partly balanced by an increase in c
arbohydrate entropy.