Implementation\nof the UNRES/SUGRES-1P Coarse-Grained\nModel of Heparin for Simulating Protein/Heparin Interactions

Heparin is a natural highly sulfated unbranched periodic\npolysaccharide\nthat plays a critical role in regulating various cellular events through\ninteractions with its protein targets such as growth factors and cytokines.\nAlthough all-atom simulations of heparin-containing systems provide\nvaluable insights into their structural and dynamical properties,\nlong chains of heparin participate in many biologically relevant processes\nat much bigger scales and longer times than the ones which all-atom\nMD is able to effectively deal with. Among these processes is the\nestablishment of chemokine gradients, amyloidogenesis, or collagen\nnetwork organization. To address this limitation, coarse-grained models\nsimplify these systems by reducing the number of degrees of freedom,\nallowing for the efficient exploration of structural changes within\nprotein/heparin complexes. We introduce and validate the accuracy\nof a new coarse-grained physics-based model designed for studying\nprotein/heparin interactions, which has been incorporated into the\nUNRES software package. The effective energy functions from UNRES\nand SUGRES-1P have been employed for the protein and heparin components,\nrespectively. A good agreement between the obtained coarse-grained\nsimulation results and experimental data confirms the suitability\nof the combined coarse-grained UNRES and SUGRES-1P model for <i>in silico</i> analysis of complex biological phenomena involving\nheparin, spanning time scales and molecular system sizes not attainable\nby conventional atomistic molecular dynamics simulations.