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...

Full description

Bibliographic Details
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/ http://irep.iium.edu.my/59249/ http://irep.iium.edu.my/59249/1/KB-sidekick.pdf http://irep.iium.edu.my/59249/7/59249_Sidekick%20for%20membrane%20simulations_SCOPUS.pdf

id	iium-59249
recordtype	eprints
spelling	iium-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 PeerReviewed 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
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
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/ http://irep.iium.edu.my/59249/ http://irep.iium.edu.my/59249/1/KB-sidekick.pdf http://irep.iium.edu.my/59249/7/59249_Sidekick%20for%20membrane%20simulations_SCOPUS.pdf
first_indexed	2023-09-18T21:23:55Z
last_indexed	2023-09-18T21:23:55Z
_version_	1777412063941885952

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

Similar Items