posted on 2024-01-04, 18:04authored byPablo
G. Garay, Matias R. Machado, Hugo Verli, Sergio Pantano
Glycans
constitute one of the most complex families of biological
molecules. Despite their crucial role in a plethora of biological
processes, they remain largely uncharacterized because of their high
complexity. Their intrinsic flexibility and the vast variability associated
with the many combination possibilities have hampered their experimental
determination. Although theoretical methods have proven to be a valid
alternative to the study of glycans, the large size associated with
polysaccharides, proteoglycans, and glycolipids poses significant
challenges to a fully atomistic description of biologically relevant
glycoconjugates. On the other hand, the exquisite dependence on hydrogen
bonds to determine glycans’ structure makes the development
of simplified or coarse-grained (CG) representations extremely challenging.
This is particularly the case when glycan representations are expected
to be compatible with CG force fields that include several molecular
types. We introduce a CG representation able to simulate a wide variety
of polysaccharides and common glycosylation motifs in proteins, which
is fully compatible with the CG SIRAH force field. Examples of application
to N-glycosylated proteins, including antibody recognition and calcium-mediated
glycan–protein interactions, highlight the versatility of the
enlarged set of CG molecules provided by SIRAH.