Evaluation and refinement of all-atom force fields for reproducing collagen structure and dynamics

Area of Science:

• Biomolecular modeling
• Structural biology
• Computational biophysics

Background:

• Collagen's XYGly motif forms the extracellular matrix skeleton, and mutations cause disease.
• Experimental study of collagen mutations is challenging, necessitating accurate computational methods.
• Proline-4(R)-hydroxyproline-glycine (POG) repeats are key collagen motifs and serve as model systems.

Purpose of the Study:

• To evaluate the accuracy of molecular dynamics force fields for modeling collagen.
• To compare simulation results with experimental data for POG homotrimers.
• To identify suitable force fields for future collagen mutation studies.

Main Methods:

• Atomistic molecular dynamics simulations of POG10 homotrimers.
• Testing of CHARMM, AMBER, and GROMOS force fields with various water models.
• Comparison of simulation data against crystal structure, NMR, and small-angle X-ray scattering (SAXS) data.

Main Results:

• AMBER and CHARMM force fields offer acceptable descriptions of collagen structure.
• AMBER force fields accurately reproduce experimental collagen dihedrals, torsions, and SAXS data.
• CHARMM force fields require CMAP term adjustments (CHARMM36mGP) to match experimental accuracy.

Conclusions:

• AMBER ff99sb or modified CHARMM36 (CHARMM36mGP) are recommended for modeling collagen-like peptides.
• Accurate force fields are essential for understanding collagen structure-function relationships.
• This work provides a basis for future simulations of collagen mutations and disease.