NMR-Based Explicit Ensemble Dynamics Simulations of Membrane Protein

Abstract

Various NMR observables, such as chemical shift anisotropy (CSA) and dipolar coupling (DC) in solid-state NMR, and residual dipolar coupling (RDC) in solution NMR experiments, have been used to characterize membrane protein structures. As time- and ensemble-averaged measurements, those observables also embed protein dynamics, which provides collective motions relevant to protein function. However, most of present NMR structure determination approaches do not consider protein-lipid interactions, which are essential determinants of membrane protein structure and function. To overcome these limitations, various NMR observables were utilized as restraints in ensemble dynamics molecular dynamics simulations to investigate protein dynamics in the explicit membranes. As representative membrane proteins, Pf1 coat protein and Fd coat protein were used to set up two model systems separately. Both of them are single-pass transmembrane helical proteins involving one membrane associated periplasmic helix. The resulting structures satisfy the NMR observables and are compared with the published structures. The disposition of protein TM helix in the explicit membrane is identified and the degree of freedom of the helix orientation under NMR restraints is observed.