Bioinspired design rules for flipping across the lipid bilayer from systematic simulations of membrane protein segments

The orientation of integral membrane proteins (IMPs) with respect to the membrane is established during protein synthesis and insertion into the membrane. After synthesis, IMP orientation is thought to be fixed due to the thermodynamic barrier for “flipping” protein loops or helices across the hydrophobic core of the membrane in a process analogous to lipid flip-flop. A notable exception is EmrE, a homodimeric IMP with an N-terminal transmembrane helix that can flip across the membrane until flipping is arrested upon dimerization. Understanding the features of the EmrE sequence that permit this unusual flipping behavior would be valuable for guiding the design of synthetic materials capable of translocating or flipping charged groups across lipid membranes. To elucidate the molecular mechanisms underlying flipping in EmrE and derive bioinspired design rules, we employ atomistic molecular dynamics simulations and enhanced sampling techniques to systematically investigate the flipping of ..., , # Data from: Bioinspired design rules for flipping across the lipid bilayer from systematic simulations of membrane protein segments

Author: ByungUk Park
Date: 7/22/2025

The following tarball file data.tar.gz contains all the data relevant to the simulations of truncated peptide systems introduced in this work ([https://doi.org/10.1039/D5ME00032G](https://doi.org/10.1039/D5ME00032G)) and scripts for the analysis of the data. First six folders ('1.Nloop', '2.Npep_E14charge', '3.Cpep', '4.Npep_E14neutral', '5.monomer_E14charge', '6.Hbond_analysis') contain input and output files for the simulations of different peptide systems (e.g., 'index.ndx', '.mdp', '.top', '.tpr', '.xtc', etc). Each of these folders follows same organization (detailed explanation in '1.Nloop' section). The remaining two folders ('misc', 'scripts') contain scripts used to analyze the simulation outputs. All simulations were run with Gromacs 2021.5 patched with PLUMED 2.8.

* Simulation-related files
* Some of the...,