Amber ff24EXP-GA, Based on Empirical Ramachandran Distributions of Glycine and Alanine Residues in Water

Molecular dynamics
(MD) offers important insights into
intrinsically
disordered peptides and proteins (IDPs) at a level of detail that
often surpasses that available through experiments. Recent studies
indicate that MD force fields do not reproduce intrinsic conformational
ensembles of amino acid residues in water well, which limits their
applicability to IDPs. We report a new MD force field, Amber ff24EXP-GA,
derived from Amber ff14SB by optimizing the backbone dihedral potentials
for guest glycine and alanine residues in cationic GGG and GAG peptides,
respectively, to best match the guest residue-specific spectroscopic
data. Amber ff24EXP-GA outperforms Amber ff14SB with respect to conformational
ensembles of all 14 guest residues x (G, A, L, V, I, F, Y, Dp, Ep, R, C, N, S, T) in GxG peptides in water, for which
complete sets of spectroscopic data are available. Amber ff24EXP-GA
captures the spectroscopic data for at least 7 guest residues (G,
A, V, F, C, T, Ep) better than CHARMM36m and exhibits more
amino acid specificity than both the parent Amber ff14SB and CHARMM36m.
Amber ff24EXP-GA reproduces the experimental data on three folded
proteins and three longer IDPs well, while outperforming Amber ff14SB
on short unfolded peptides.