Benchmark of Available Explicit Solvent Models in CHARMM36m to Characterize Glycosaminoglycans

Area of Science:

• Biochemistry
• Computational Chemistry
• Structural Biology

Background:

• Heparin (HP), a highly sulfated glycosaminoglycan (GAG), plays vital roles in biological processes.
• HP's functions are mediated by electrostatic interactions with proteins.
• The CHARMM36m force field is used for GAG simulations, but solvent effects are unclear.

Purpose of the Study:

• To investigate the influence of explicit solvent models on heparin dodecamer structure.
• To evaluate the performance of the CHARMM36m force field with different water models for GAG simulations.

Main Methods:

• Conducted 5 μs molecular dynamics simulations of a heparin dodecamer.
• Employed five explicit solvent models: TIP3P, TIP4P, TIP5P, SPC/E, and OPC.
• Compared simulation results with the GLYCAM06 force field.

Main Results:

• TIP3P and SPC/E models produced stable HP conformations.
• TIP4P, TIP5P, and OPC models led to increased structural variability.
• CHARMM36m generally preserved HP global structure but differed in glycosidic linkage sampling compared to GLYCAM06.

Conclusions:

• The choice of water model critically affects the conformational dynamics of heparin.
• Findings provide guidance for selecting appropriate water models in GAG simulations.
• Accurate simulation of sulfated carbohydrates requires careful consideration of solvent representation.