Molecular dynamics simulation is a powerful biophysical tool to gain theoretical insights into protein action. In mechanobiology, conformational change of bacterial mechanosensitive ion channels has been studied extensively. Here we studied transient receptor potential cation channel subfamily V member 2 (TRPV2), a mammalian mechanosensitive ion channel, using coarse grained molecular dynamics simulation. Coarse grained geometry of TRPV2 was generated based on a full atomic cryo-electron microscopy structure (PDB ID: 5HI9). The TRPV2 protein was embedded in a membrane composed of POPC/POPS phospholipid bilayer and solvated. The structure of TRPV2 homotetramer was stable during 1 μs simulation period. While a bacterial mechanosensitive channel MscS showed significant increase in pore radius in response to membrane tension, TRPV2 did not, as suggested by previous experimental studies. Transmembrane helix tilt, which was observed in mechanosensitive opening of MscS, was not observed in TRPV2 in membrane tension. This result suggests that mechanosensitive alteration of TRPV2 structure requires external force other than the membrane tension.
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Coarse grained molecular dynamic simulation of mammalian mechanosensitive ion channel TRPV2
1. Coarse grained molecular dynamic simulation of
mammalian mechanosensitive ion channel TRPV2
Ken Takahashi, Keiji Naruse
Department of Cardiovascular Physiology
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences
Okayama University
ISMB 2017, Singapore, Dec 14
2. Molecular dynamics (MD) simulation
MscL
MscS
)cos(1)(V
)cos()cos(
2
1
)(V
)(
2
1
)(V
4
)(V
4)(V
dddihedral
2
aaangle
2
bbbond
0
el
612
Jones-Lennard
ijklijkl
ijkijk
ijij
ijrel
ji
ij
ij
ij
ij
ij
ijij
nK
K
ddKd
r
qq
r
rr
r
Potential energy functions:
14. Conclusion
1. TRPV2 transmembrane helices were stable against lipid
bilayer tension.
2. Pore radius of TRPV2 channel did not increase in response to
lipid bilayer tension.
3. Interactions between helices/lipids may determine the
mechanosensitive behavior of TRPV2 channel.
15. Acknowledgment
Nagoya University
Yuichiro Imaichi
Tatsuro Yokoyama
Okayama University
Kensaku Toda
Kazuya Saruwatari
Yutaka Kuriyama
Keiji Naruse
This study was supported by Grant-in-Aid for Scientific Research on
Innovative Areas, No. 15H05936.
Notes de l'éditeur
MODELLER is used for homology or comparative modeling of protein three-dimensional structures (1,2). The user provides an alignment of a sequence to be modeled with known related structures and MODELLER automatically calculates a model containing all non-hydrogen atoms. MODELLER implements comparative protein structure modeling by satisfaction of spatial restraints (3,4), and can perform many additional tasks, including de novo modeling of loops in protein structures, optimization of various models of protein structure with respect to a flexibly defined objective function, multiple alignment of protein sequences and/or structures, clustering, searching of sequence databases, comparison of protein structures, etc. MODELLER is available for download for most Unix/Linux systems, Windows, and Mac.
Modeller was developed by UCSF.
PDB ID: 5HI9
homotetramer
MODELLER is used for homology or comparative modeling of protein three-dimensional structures (1,2). The user provides an alignment of a sequence to be modeled with known related structures and MODELLER automatically calculates a model containing all non-hydrogen atoms. MODELLER implements comparative protein structure modeling by satisfaction of spatial restraints (3,4), and can perform many additional tasks, including de novo modeling of loops in protein structures, optimization of various models of protein structure with respect to a flexibly defined objective function, multiple alignment of protein sequences and/or structures, clustering, searching of sequence databases, comparison of protein structures, etc. MODELLER is available for download for most Unix/Linux systems, Windows, and Mac.
Modeller was developed by UCSF.
