The Assessment of MD Force Fields with Respect to Alanine Conformations in Aqueous Solutions*

The ability to reproduce conformational ensembles of the central alanine residue in GAG and AAA obtained from experimentally-derived φ- and ψ-dependent J coupling constants and amide I’ profiles is examined for six molecular dynamics (MD) force fields (Amber ff14SB, Amber ff99SBnmr1, Amber ff03ws, OPLS-AA/L, OPLS-AA/M, and CHARMM36). Compared to the empirical Gaussian model, which is constructed to best fit the experimental data, MD-derived Ramachandran plots produce overly constricted polyproline II (pPII) basin, an overpopulated antiparallel β basin, and an underpopulated transitional β basin. Our results show that Amber ff14SB best reproduces the experimental J coupling constants and yields the highest pPII populations of the central alanine residue in GAG (55%) and AAA (63%), in a good agreement with the the Gaussian model (59% and 76%). The comparision between experimental and MD-derived results for GAG in water is extended to various water/ethanol mixtures in order to further evaluate Amber ff14SB, CHARMM36, and OPLS-AA/M. Amber ff14SB again outperforms CHARMM36 and OPLS-AA/M in reproducing experimental J coupling constants and amide I’ profiles.