Abstract
Heparin/heparan sulfates (H/HS) are ubiquitous biopolymers that interact with many proteins to induce a range of biological functions. Unfortunately, how these biopolymers recognize their preferred protein targets remain poorly understood. It is suggested that computational simulations offer attractive avenues but a number of challenges, e.g., difficulty of selecting a comprehensive force field, few simple tools to interpret data, among others, remain. This work addresses several such challenges so as to help ease the implementation and analysis of computational experiments. First, this work presents a rigorous comparison of two different recent force fields, CHARMM36 and GLYCAM06, for H/HS studies. Second, it introduces two new straightforward parameters, i.e., end-to-end distance and minimum volume enclosing ellipsoid, to understand the myriad conformational forms of oligosaccharides that evolve over time in water. Third, it presents an application to elucidate the number and nature of inter and intramolecular, nondirect bridging water molecules, which help stabilize unique forms of H/HS. The results show that nonspecialists can use either CHARMM36 or GLYCAM06 force fields because both gave comparable results, albeit with small differences. The comparative study shows that the HS hexasaccharide samples a range of conformations with nearly equivalent energies, which could be the reason for its recognition by different proteins. Finally, analysis of the nondirect water bridges across the dynamics trajectory shows their importance in stabilization of certain conformational forms, which may become important for protein recognition. Overall, the work aids nonspecialists employ computational studies for understanding the solution behavior of H/HS.