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Sidekick for membrane simulations: automated ensemble molecular dynamics simulations of transmembrane helices

The 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 st...

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Main Authors: Hall, Benjamin A., Abd Halim, Khairul Bariyyah, Buyan, Amanda, S.P Sansom, Mark
Format: Article
Language:English
English
Published: 2014
Subjects:
Q Science (General)
Online Access:http://irep.iium.edu.my/59249/1/KB-sidekick.pdf
http://irep.iium.edu.my/59249/7/59249_Sidekick%20for%20membrane%20simulations_SCOPUS.pdf
http://irep.iium.edu.my/59249/
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spelling my.iium.irep.592492017-11-14T03:21:15Z http://irep.iium.edu.my/59249/ Sidekick for membrane simulations: automated ensemble molecular dynamics simulations of transmembrane helices Hall, Benjamin A. Abd Halim, Khairul Bariyyah Buyan, Amanda S.P Sansom, Mark Q Science (General) The 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. 2014-05-13 Article REM application/pdf en http://irep.iium.edu.my/59249/1/KB-sidekick.pdf application/pdf en http://irep.iium.edu.my/59249/7/59249_Sidekick%20for%20membrane%20simulations_SCOPUS.pdf Hall, Benjamin A. and Abd Halim, Khairul Bariyyah and Buyan, Amanda and S.P Sansom, Mark (2014) Sidekick for membrane simulations: automated ensemble molecular dynamics simulations of transmembrane helices. Journal of Chemical Theory and Computation. pp. 2165-2175. 10.1021/ct500003g
institution Universiti Islam Antarabangsa Malaysia
building IIUM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider International Islamic University Malaysia
content_source IIUM Repository (IREP)
url_provider http://irep.iium.edu.my/
language English
English
topic Q Science (General)
spellingShingle Q Science (General)
Hall, Benjamin A.
Abd Halim, Khairul Bariyyah
Buyan, Amanda
S.P Sansom, Mark
Sidekick for membrane simulations: automated ensemble molecular dynamics simulations of transmembrane helices
description The 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.
format Article
author Hall, Benjamin A.
Abd Halim, Khairul Bariyyah
Buyan, Amanda
S.P Sansom, Mark
author_facet Hall, Benjamin A.
Abd Halim, Khairul Bariyyah
Buyan, Amanda
S.P Sansom, Mark
author_sort Hall, Benjamin A.
title Sidekick for membrane simulations: automated ensemble molecular dynamics simulations of transmembrane helices
title_short Sidekick for membrane simulations: automated ensemble molecular dynamics simulations of transmembrane helices
title_full Sidekick for membrane simulations: automated ensemble molecular dynamics simulations of transmembrane helices
title_fullStr Sidekick for membrane simulations: automated ensemble molecular dynamics simulations of transmembrane helices
title_full_unstemmed Sidekick for membrane simulations: automated ensemble molecular dynamics simulations of transmembrane helices
title_sort sidekick for membrane simulations: automated ensemble molecular dynamics simulations of transmembrane helices
publishDate 2014
url http://irep.iium.edu.my/59249/1/KB-sidekick.pdf
http://irep.iium.edu.my/59249/7/59249_Sidekick%20for%20membrane%20simulations_SCOPUS.pdf
http://irep.iium.edu.my/59249/
_version_ 1643615543860658176
score 13.211869

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