Protocol To Make Protein NMR Structures Amenable to Stable Long Time Scale Molecular Dynamics Simulations.

A robust protocol for the treatment of NMR protein structures is presented that makes them amenable to long time scale molecular dynamics (MD) simulations that are stable. The protocol embeds an NMR structure in a native low energy region of the recently developed ff99SB_φψ(g24;CS) molecular mechanics force field. Extended MD trajectories that start from these structures show good consistency with proton-proton nuclear Overhauser effect data, and they reproduce NMR chemical shift data better than the original NMR structures as is demonstrated for four protein systems. Moreover, for all proteins studied here the simulations spontaneously approach the X-ray crystal structures, thereby improving the effective resolution of the initial structural models.