Conformational Dynamics of Two Natively Unfolded Fragment Peptides: Comparison of the AMBER and CHARMM Force Fields.

Physics-based force fields are the backbone of molecular dynamics simulations. In recent years, significant progress has been made in the assessment and improvement of commonly used force fields for describing conformational dynamics of folded proteins. However, the accuracy for the unfolded states remains unclear. The latter is however important for detailed studies of protein folding pathways, conformational transitions involving unfolded states, and dynamics of intrinsically disordered proteins. In this work, we compare the three commonly used force fields, AMBER ff99SB-ILDN, CHARMM22/CMAP, and CHARMM36, for modeling the natively unfolded fragment peptides, NTL9(1–22) and NTL9(6–17), using explicit-solvent replica-exchange molecular dynamics simulations. All three simulations show that NTL9(6–17) is completely unstructured, while NTL9(1–22) transiently samples various β-hairpin states, reminiscent of the first β-hairpin in the structure of the intact NTL9 protein. The radius of gyration of the two pept...