All-atom molecular dynamics simulations using orientational constraints from anisotropic NMR samples

Abstract

Orientational constraints obtained from solid state NMR experiments on anisotropic samples are used here in molecular dynamics (MD) simulations for determining the structure and dynamics of several different membrane-bound molecules. The new MD technique is based on the inclusion of orientation dependent pseudoforces in the COSMOS-NMR force field. These forces drive molecular rotations and re-orientations in the simulation, such that the motional time-averages of the tensorial NMR properties approach the experimentally measured parameters. The orientational-constraint-driven MD simulations are universally applicable to all NMR interaction tensors, such as chemical shifts, dipolar couplings and quadrupolar interactions. The strategy does not depend on the initial choice of coordinates, and is in principle suitable for any flexible molecule. To test the method on three systems of increasing complexity, we used as constraints some deuterium quadrupolar couplings from the literature on pyrene, cholesterol and an antimicrobial peptide embedded in oriented lipid bilayers. The MD simulations were able to reproduce the NMR parameters within experimental error. The alignment of the three membranebound molecules and some aspects of their conformation were thus derived from the NMR data, in good agreement with previous analyses. Furthermore, the new approach yielded for the first time the distribution of segmental orientations with respect to the membrane and the order parameter tensors of all three systems.

Tilt and Azimuthal Angles of a Transmembrane Peptide: A Comparison between Molecular Dynamics Calculations and Solid-State NMR Data of Sarcolipin in Lipid Membranes

“…Subsequently, Roux and co-workers applied this combined MD/NMR approach to understand the structural dynamics of several other membrane proteins and peptides in various lipid environments (101,104). More recently, MD simulations have been used with success to study the structural dynamics and membrane interactions of antimicro-bial peptides (106,107). From these studies emerged excellent agreements between experimental and calculated NMR parameters (CSA and DC), which made it possible to reproduce the topologies and lipid interactions of these membrane-embedded polypeptides.…”

Orientation and Order of the Amide Group of Sphingomyelin in Bilayers Determined by Solid-State NMR

“…As described above, if the wobbling motion of the rotation axis is anisotropic, Saupe order tensor analysis using S zz and S xx ÀS yy values should be adopted (32), and therefore the approximation using a single order parameter S (i.e., the S xx ÀS yy value is ignored) would provide much larger RMSD values.…”

When detergent meets bilayer: Birth and coming of age of lipid bicelles

“…As described, the 1 H– 13 C-PELF method gives equivalent results and does not require isotope labeling and does not suffer from the sensitivity and assignment problems imposed by 2 H-labeled phospholipids. A promising extension would be the use of order parameters as orientational angular constraints in molecular dynamics simulations [197]. …”