Comparing Molecular Dynamics Simulations with Solid-State NMR Data

We report molecular dynamics simulations in the explicit membrane environment of a small membrane-embedded protein, sarcolipin, which regulates the sarcoplasmic reticulum Ca-ATPase activity in both cardiac and skeletal muscle. In its monomeric form, we found that sarcolipin adopts a helical conformation, with a computed average tilt angle of 28 +/- 6 degrees and azymuthal angles of 66 +/- 22 degrees, in reasonable accord with angles determined experimentally (23 +/- 2 degrees and 50 +/- 4 degrees, respectively) using solid-state NMR with separated-local-field experiments. The effects of time and spatial averaging on both (15)N chemical shift anisotropy and (1)H/(15)N dipolar couplings have been analyzed using short-time averages of fast amide out-of-plane motions and following principal component dynamic trajectories. We found that it is possible to reproduce the regular oscillatory patterns observed for the anisotropic NMR parameters (i.e., PISA wheels) employing average amide vectors. This work highlights the role of molecular dynamics simulations as a tool for the analysis and interpretation of solid-state NMR data.

Simulated CSA and DC values obtained for residue 25 from MD trajectories of the last 140 ns of simulations. (A) Overlay of the calculated PISEMA spectra from SLN snapshots taken from MD trajectories. The distribution of the CSA and DC values is indicated on each axis. (B–D) Three-dimensional plot showing the distribution of CSA and DC for residue 25 with no torsion-angle averaging (B), with 10-ps torsion-angle averaging (C), and with 20-ps torsion-angle averaging (D).