Benchmarking Adaptive Steered Molecular Dynamics (ASMD) on CHARMM Force Fields

The potentials of mean force (PMFs) along the end‐to‐end distance of two different helical peptides have been obtained and benchmarked using the adaptive steered molecular dynamics (ASMD) method. The results depend strongly on the choice of force field driving the underlying all‐atom molecular dynamics, and are reported with respect to the three most popular CHARMM force field versions: c22, c27 and c36. Two small peptides, ALA10 and 1PEF, serve as the particular case studies. The comparisons between the versions of the CHARMM force fields provides both a qualitative and quantitative look at their performance in forced unfolding simulations in which peptides undergo large changes in structural conformations. We find that ASMD with the underlying c36 force field provides the most robust results for the selected benchmark peptides. Adaptive steered molecular dynamics method (ASMD) is used to mechanically unfold the α‐helix 1PEF (green ribbon) as its end‐to‐end distance (ree, the pulling coordinate) is gradually increased from 22 to 62 Å. The solid black lines represent the work for each trajectory, W(ζti ), in several stages whose average (thick‐red‐highlighted black‐dashed curve) represents the overall PMF, W‾ . We found that CHARMM36 produced the most accurate result among various CHARMM variants.