SIRAH late harvest: parameterization of coarse-grained glycans

GARAY, PABLO G.; PANTANO, SERGIO

San Luis Capital

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; 2019

Sociedad Argentina de Biofísica

Glycans are one of the most structurally and functionally diverse molecules in nature. Their structures range from simple mono or disaccharides to more complex structures like chains, branched structures, oligosaccharides or polysaccharides, and could bond to other biological molecules like proteins and lipids to form glycoproteins and glycolipids. One of the principal tools to complement experimental studies is the use of molecular dynamics (MD) simulation. Nevertheless, the computational cost of simulating large glycosylated proteins or chains with realistically long polysaccharides with polymerization degrees in the order of 10 5 poses significant challenges to fully atomistic MD simulations. A workaround to this limitation is the development of coarse grain (CG) models. CG representations reduce the number of atoms in the system making them less computational demanding but still preserving salient features of the molecules of interest. Our group develops the SIRAH force field ( Southamerican Initiative for a Rapid and Accurate Hamiltonian, www.sirahff.com) which contains parameters for DNA, proteins, solvents, ions, and lipids. Here, show the development of the first glycan model at the CG level that allows simulations of polysaccharides and/or glycosylated proteins in an unbiased and consistent manner. Moreover, we provide a fully generalizable coarse-graining rule that can be expanded to virtually any six-membered ring (pyranoses) including functionalizations and ramifications. Examples of applications include oligosaccharides, cellulose fibers, pentobiose binding to the carbohydrate-binding module (CBM), and antibody recognition by N-glycosylated proteins. Ours results from cellobiose, deca-b-D-Glcp 1-4, cellulose I alfa and beta, and pentobiose binding to CBM demonstrate that with this parametrization the same molecule can have different behaviors depending on the study system. The result from the N-glycosylation shows that is possible to use this post-translational modification in different situations. These new moieties considerably expand the range of molecular systems amenable to be studied with CG force field.