Certification of Molecular Dynamics Trajectories with NMR Chemical Shifts

Molecular dynamics ensembles of proteins generated by different force fields (AMBER ff99, ff99SB, ff03) have been quantitatively assessed based on their back-calculated Cα, Cβ, and C′ chemical shifts in comparison with NMR experiments. For the latest generation of force fields, a substantial improvement is found for ensemble-averaged chemical shifts over individual snapshots. Explicit inclusion of protein dynamics provides the largest improvement for Cβ chemical shifts, which are dominated by φ, ψ, and χ 1 dihedral angle distributions. Since NMR chemical shifts are available for a vast number of proteins, this novel strategy opens up the possibility to quantitatively certify molecular dynamics simulations on an unprecedented scale.