g_membed: Efficient insertion of a membrane protein into an equilibrated lipid bilayer with minimal perturbation

To efficiently insert a protein into an equilibrated and fully hydrated membrane with minimal membrane perturbation we present a computational tool, called g_membed, which is part of the Gromacs suite of programs. The input consists of an equilibrated membrane system, either flat or curved, and a protein structure in the right position and orientation with respect to the lipid bilayer. g_membed first decreases the width of the protein in the xy‐plane and removes all molecules (generally lipids and waters) that overlap with the narrowed protein. Then the protein is grown back to its full size in a short molecular dynamics simulation (typically 1000 steps), thereby pushing the lipids away to optimally accommodate the protein in the membrane. After embedding the protein in the membrane, both the lipid properties and the hydration layer are still close to equilibrium. Thus, only a short equilibration run (less then 1 ns in the cases tested) is required to re‐equilibrate the membrane. Its simplicity makes g_membed very practical for use in scripting and high‐throughput molecular dynamics simulations. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2010

[1]  W. Delano The PyMOL Molecular Graphics System , 2002 .

[2]  Camilo Aponte-Santamaría,et al.  Crystal Structure of a Yeast Aquaporin at 1.15 Å Reveals a Novel Gating Mechanism , 2009, PLoS biology.

[3]  T. Darden,et al.  Particle mesh Ewald: An N⋅log(N) method for Ewald sums in large systems , 1993 .

[4]  Robert Vácha,et al.  Biomolecular simulations of membranes: physical properties from different force fields. , 2008, The Journal of chemical physics.

[5]  Syma Khalid,et al.  Coarse-grained MD simulations of membrane protein-bilayer self-assembly. , 2008, Structure.

[6]  E. Carpenter,et al.  Overcoming the challenges of membrane protein crystallography , 2008, Current opinion in structural biology.

[7]  Chungho Kim,et al.  The structure of the integrin αIIbβ3 transmembrane complex explains integrin transmembrane signalling , 2009, The EMBO journal.

[8]  O. Berger,et al.  Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. , 1997, Biophysical journal.

[9]  R. Friesner,et al.  Evaluation and Reparametrization of the OPLS-AA Force Field for Proteins via Comparison with Accurate Quantum Chemical Calculations on Peptides† , 2001 .

[10]  B. Roux,et al.  Structure, energetics, and dynamics of lipid–protein interactions: A molecular dynamics study of the gramicidin A channel in a DMPC bilayer , 1996, Proteins.

[11]  G. Heijne,et al.  Genome‐wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms , 1998, Protein science : a publication of the Protein Society.

[12]  Thomas Huber,et al.  G protein-coupled receptors self-assemble in dynamics simulations of model bilayers. , 2007, Journal of the American Chemical Society.

[13]  Christian Kandt,et al.  Setting up and running molecular dynamics simulations of membrane proteins. , 2007, Methods.

[14]  Semen O. Yesylevskyy,et al.  ProtSqueeze: Simple and Effective Automated Tool for Setting up Membrane Protein Simulations , 2007, J. Chem. Inf. Model..

[15]  Graham R. Smith,et al.  Setting up and optimization of membrane protein simulations , 2002, European Biophysics Journal.

[16]  H. Berendsen,et al.  Interaction Models for Water in Relation to Protein Hydration , 1981 .

[17]  R. Walser,et al.  A minimal transmembrane beta-barrel platform protein studied by nuclear magnetic resonance. , 2007, Biochemistry.

[18]  W. L. Jorgensen,et al.  Comparison of simple potential functions for simulating liquid water , 1983 .

[19]  Eric J. Sorin,et al.  Exploring the helix-coil transition via all-atom equilibrium ensemble simulations. , 2005, Biophysical journal.

[20]  John P. Overington,et al.  How many drug targets are there? , 2006, Nature Reviews Drug Discovery.

[21]  Christian Kandt,et al.  Membrane protein simulations with a united-atom lipid and all-atom protein model: lipid–protein interactions, side chain transfer free energies and model proteins , 2006, Journal of physics. Condensed matter : an Institute of Physics journal.

[22]  E. Lindahl,et al.  3D pressure field in lipid membranes and membrane-protein complexes. , 2009, Physical review letters.

[23]  Berk Hess,et al.  LINCS: A linear constraint solver for molecular simulations , 1997 .

[24]  L. Shen,et al.  Transmembrane helix structure, dynamics, and interactions: multi-nanosecond molecular dynamics simulations. , 1997, Biophysical journal.

[25]  P. Biggin,et al.  Molecular dynamics simulations of membrane proteins. , 2008, Methods in molecular biology.

[26]  J Deisenhofer,et al.  Crystallographic refinement at 2.3 A resolution and refined model of the photosynthetic reaction centre from Rhodopseudomonas viridis. , 1989, Journal of molecular biology.

[27]  M. Parrinello,et al.  Canonical sampling through velocity rescaling. , 2007, The Journal of chemical physics.

[28]  Carsten Kutzner,et al.  GROMACS 4:  Algorithms for Highly Efficient, Load-Balanced, and Scalable Molecular Simulation. , 2008, Journal of chemical theory and computation.

[29]  H. Berendsen,et al.  Molecular dynamics with coupling to an external bath , 1984 .