Modeling the conformational heterogeneity of poly- and oligosaccharides requires proper sampling of the accessible conformations, classification of the conformations and accurate treatment of the energies and forces as a function of conformation.  Towards these needs we have developed enhanced sampling Hamiltonian Replica Exchange methods specifically designed for carbohydrates that combine solute tempering (REST2) with biasing potentials acting on the glycosidic linkages implemented using the CMAP approach (bpCMAP).  This method has been successfully applied to complex carbohydrates ranging from di- and trisaccharides to the glycan shield of the HIV Envelope.  To facilitate the analysis of the bpCMAP REST2 simulation results we’ve developed approaches based on the clustering of conformations in the context of the glycosidic linkages (GL clusters) and the use of overlap coefficients describing the extent of spatial overlap of the volumes sampled by full glycans as well as their constituent monosaccharides..   Results will be presented for studies using the additive CHARMM36 carbohydrate force field.  In addition, progress towards a polarizable force field for carbohydrates based on the classical Drude oscillator will be presented.

Modeling the conformational heterogeneity of complex carbohydrates: Enhanced sampling, methods of analyses and towards a polarizable force field

254th National Meeting (2017)

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