SIRAH Late Harvest: Coarse-Grained Models for Protein Glycosylation

GARAY, PABLO G.; MACHADO, MATIAS R.; VERLI, HUGO; PANTANO, SERGIO

JOURNAL OF CHEMICAL THEORY AND COMPUTATION

AMER CHEMICAL SOC

Año: 2024

1549-9618

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.