@article{ISI:000404914200024,
 abstract = {Pore forming toxins (PFTs) are virulent proteins whose primary goal is
to lyse target cells by unregulated pore formation. Molecular dynamics
simulations can potentially provide molecular insights on the properties
of the pore complex as well as the underlying pathways for pore
formation. In this manuscript we compare both coarse-grained (MARTINI
force-field) and all-atom simulations, and comment on the accuracy of
the MARTINI coarse-grained method for simulating these large membrane
protein pore complexes. We report 20 long coarse-grained MARTINI
simulations of prototypical pores from two different classes of pore
forming toxins (PFTs) in lipid membranes - Cytolysin A (ClyA), which is
an example of an toxin, and -hemolysin (AHL) which is an example of a
toxin. We compare and contrast structural attributes such as the root
mean square deviation (RMSD) histograms and the inner pore radius
profiles from the MARTINI simulations with all-atom simulations. RMSD
histograms sampled by the MARTINI simulations are about a factor of 2
larger, and the radius profiles show that the transmembrane domains of
both ClyA and AHL pores undergo significant distortions, when compared
with the all-atom simulations. In addition to the fully inserted
transmembrane pores, membrane-inserted proteo-lipid ClyA arcs show large
shape distortions with a tendency to close in the MARTINI simulations.
While this phenomenon could be biologically plausible given the fact
that -toxins can form pores of varying sizes, the additional flexibility
is probably due to weaker inter-protomer interactions which are
modulated by the elastic dynamic network in the MARTINI force-field. We
conclude that there is further scope for refining inter-protomer
contacts and perhaps membrane-protein interactions in the MARTINI
coarse-grained framework. A robust coarse-grained force-field will
enable one to reliably carry out mesoscopic simulations which are
required to understand protomer oligomerization, pore formation and
leakage.},
 author = {Desikan, Rajat and Patra, Swarna M. and Sarthak, Kumar and Maiti, Prabal
K. and Ayappa, K. G.},
 doi = {10.1007/s12039-017-1316-0},
 eissn = {0973-7103},
 issn = {0974-3626},
 journal = {JOURNAL OF CHEMICAL SCIENCES},
 month = {JUL},
 number = {7, SI},
 orcid-numbers = {Maiti, Prabal/0000-0002-9956-1136
P, swarna M/0000-0001-8271-3423
Desikan, Rajat/0000-0002-0785-8187},
 pages = {1017-1030},
 researcherid-numbers = {Maiti, Prabal/B-6335-2009
P, swarna M/P-6378-2016
},
 times-cited = {9},
 title = {Comparison of coarse-grained (MARTINI) and atomistic molecular dynamics
simulations of and toxin nanopores in lipid membranes},
 unique-id = {ISI:000404914200024},
 volume = {129},
 year = {2017}
}