Transmembrane Helix Orientation and Dynamics Examined by Ensemble Dynamics with Solid-State NMR Observables and Potential of Mean Force Calculations

Abstract

Solid-state NMR (SSNMR) experiment is a very powerful technique to describe the orientation of membrane proteins and peptides in their native membrane bilayer environments. Such orientational description is invaluable since the function of membrane proteins and peptides involves a conformational change that often associates with their orientational changes. However, the present models used to interpret the SSNMR observables are rather static, and, in consequence, important motional information can be missing. In this work, we have investigated the orientation of single-pass transmembrane domain of virus protein “u” (Vpu) from HIV-1 by determining ensemble of structures using multiple conformer models. The resulting ensemble of structures showed significantly larger fluctuations in their orientation while averaged orientation maintained the compatible value with the static model. Further, we have compared the SSNMR ensemble dynamics results with the Vpu orientation from the molecular dynamics simulations and helix-tilt free energy calculations in explicit membranes.