ct500003g_si_002.mp4 (15.24 MB)
Sidekick for Membrane Simulations: Automated Ensemble Molecular Dynamics Simulations of Transmembrane Helices
media
posted on 2014-05-13, 00:00 authored by Benjamin
A. Hall, Khairul Bariyyah Abd Halim, Amanda Buyan, Beatrice Emmanouil, Mark S. P. SansomThe interactions of transmembrane
(TM) α-helices with the
phospholipid membrane and with one another are central to understanding
the structure and stability of integral membrane proteins. These interactions
may be analyzed via coarse grained molecular dynamics (CGMD) simulations.
To obtain statistically meaningful analysis of TM helix interactions,
large (N ca. 100) ensembles of CGMD simulations are needed. To facilitate
the running and analysis of such ensembles of simulations, we have
developed Sidekick, an automated pipeline software for performing
high throughput CGMD simulations of α-helical peptides in lipid
bilayer membranes. Through an end-to-end approach, which takes as
input a helix sequence and outputs analytical metrics derived from
CGMD simulations, we are able to predict the orientation and likelihood
of insertion into a lipid bilayer of a given helix of a family of
helix sequences. We illustrate this software via analyses of insertion
into a membrane of short hydrophobic TM helices containing a single
cationic arginine residue positioned at different positions along
the length of the helix. From analyses of these ensembles of simulations,
we estimate apparent energy barriers to insertion which are comparable
to experimentally determined values. In a second application, we use
CGMD simulations to examine the self-assembly of dimers of TM helices
from the ErbB1 receptor tyrosine kinase and analyze the numbers of
simulation repeats necessary to obtain convergence of simple descriptors
of the mode of packing of the two helices within a dimer. Our approach
offers a proof-of-principle platform for the further employment of
automation in large ensemble CGMD simulations of membrane proteins.
History
Usage metrics
Categories
Keywords
Transmembrane HelicesThe interactionsTM helicesthroughput CGMD simulationsTM helix interactionsintegral membrane proteinsCGMD simulationsErbB 1 receptor tyrosine kinasecationic arginine residueensemble CGMD simulationsAutomated Ensemble Molecular Dynamics Simulationsuse CGMD simulationslipid bilayer membranes