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.