RT Journal Article
SR Electronic
T1 Extending the Martini coarse-grained forcefield to N-glycans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.05.08.085399
DO 10.1101/2020.05.08.085399
A1 Aishwary T. Shivgan
A1 Jan K. Marzinek
A1 Roland G. Huber
A1 Alexander Krah
A1 Richard H. Henchman
A1 Paul Matsudaira
A1 Chandra S. Verma
A1 Peter J. Bond
YR 2020
UL http://biorxiv.org/content/early/2020/05/10/2020.05.08.085399.abstract
AB Glycans play a vital role in a large number of cellular processes. Their complex and flexible nature hampers structure-function studies using experimental techniques. Molecular dynamics (MD) simulations can help in understanding dynamic aspects of glycans if the forcefield (FF) parameters used can reproduce key experimentally observed properties. Here, we present optimized coarse-grained (CG) Martini FF parameters for N-glycans, calibrated against experimentally derived binding affinities for lectins. The CG bonded parameters were obtained from atomistic (ATM) simulations for different glycan topologies including high mannose and complex glycans with various branching patterns. In the CG model, additional elastic networks are shown to improve maintenance of the overall conformational distribution. Solvation free energies and octanol-water partition coefficients were also calculated for various n-glycan disaccharide combinations. When using standard Martini non-bonded parameters, we observed that glycans spontaneously aggregated in the solution and required down-scaling of their interactions for reproduction of ATM model radial distribution functions. We also optimised the non-bonded interactions for glycans interacting with seven lectin candidates and show that scaling down the glycan-protein interactions can reproduce free energies obtained from experimental studies. These parameters should be of use in studying the role of glycans in various glycoproteins, carbohydrate binding proteins (CBPs) as well as their complexes, while benefiting from the efficiency of CG sampling.Competing Interest StatementThe authors have declared no competing interest.