Extension of the SUGRES-1P Coarse-Grained Model of Polysaccharides to Heparin

Heparin is an unbranched periodic polysaccharide composedof negativelycharged monomers and involved in key biological processes, includinganticoagulation, angiogenesis, and inflammation. Its structure anddynamics have been studied extensively using experimental as wellas theoretical approaches. The conventional approach of computationalchemistry applied to the analysis of biomolecules is all-atom moleculardynamics, which captures the interactions of individual atoms by solvingNewton's equation of motion. An alternative is molecular dynamicssimulations using coarse-grained models of biomacromolecules, whichoffer a reduction of the representation and consequently enable usto extend the time and size scale of simulations by orders of magnitude.In this work, we extend the UNIfied COarse-gRaiNed (UNICORN) modelof biological macromolecules developed in our laboratory to heparin.We carried out extensive tests to estimate the optimal weights ofenergy terms of the effective energy function as well as the optimalDebye-Hu''ckel screening factor for electrostatic interactions.We applied the model to study unbound heparin molecules of polymerizationdegree ranging from 6 to 68 residues. We compare the obtained coarse-grainedheparin conformations with models obtained from X-ray diffractionstudies of heparin. The SUGRES-1P force field was able to accuratelypredict the general shape and global characteristics of heparin molecules.