TY - JOUR
T1 - Electrostatic properties of the mechanosensitive channel of small conductance MscS
AU - Sotomayor, Marcos
AU - Van Der Straaten, Trudy A.
AU - Ravaioli, Umberto
AU - Schulten, Klaus
N1 - This work was supported by the National Institutes of Health (NIH grant No. P41 RR05969, NIH grant No. 1 RO1 GM067887, and NIH grant No. R01-GM073655), by the National Science Foundation (Network for Computational Nanotechnology grant No. EEC-0228390), and by the National Center for Supercomputing Applications. The authors also acknowledge computer time provided by the National Science Foundation (National Resource Allocation committee grant No. MCA93S028).
PY - 2006/5
Y1 - 2006/5
N2 - The mechanosensitive channel of small conductance (MscS) belongs to a family of membrane proteins that are gated in response to changes in membrane tension, thereby protecting the cell from hypo-osmotic shock. Here we report on passive ion transport simulations of MscS in a POPC bilayer using a coarse-grained particle-based description based on the Boltzmann transport Monte Carlo method. Single channel current-voltage curves are computed over hundreds of nanoseconds for channel conformations derived from all-atom molecular dynamics simulations reaching an overall simulation time of over 5 μs. Channel conformations similar to that of the crystal structure exhibit low conductance, whereas conformations reached after opening the channel by means of steered molecular dynamics simulations match experimentally determined conductances. However, while experiments indicate a slight preference for anionic currents, the simulated channel strongly selects anions over cations and the direction of rectification at high voltages is opposite to what is observed in experiments. Three-dimensional maps of time-averaged ion distribution and equilibrium occupancy profiles constructed from trajectory data indicate separation of anions and cations inside and in the immediate vicinity of the large cytoplasmic domain of MscS, in accordance with earlier molecular dynamics simulations. This separation arises from the distribution of ionizable residues of MscS and suggests a specific, yet unknown, functional purpose.
AB - The mechanosensitive channel of small conductance (MscS) belongs to a family of membrane proteins that are gated in response to changes in membrane tension, thereby protecting the cell from hypo-osmotic shock. Here we report on passive ion transport simulations of MscS in a POPC bilayer using a coarse-grained particle-based description based on the Boltzmann transport Monte Carlo method. Single channel current-voltage curves are computed over hundreds of nanoseconds for channel conformations derived from all-atom molecular dynamics simulations reaching an overall simulation time of over 5 μs. Channel conformations similar to that of the crystal structure exhibit low conductance, whereas conformations reached after opening the channel by means of steered molecular dynamics simulations match experimentally determined conductances. However, while experiments indicate a slight preference for anionic currents, the simulated channel strongly selects anions over cations and the direction of rectification at high voltages is opposite to what is observed in experiments. Three-dimensional maps of time-averaged ion distribution and equilibrium occupancy profiles constructed from trajectory data indicate separation of anions and cations inside and in the immediate vicinity of the large cytoplasmic domain of MscS, in accordance with earlier molecular dynamics simulations. This separation arises from the distribution of ionizable residues of MscS and suggests a specific, yet unknown, functional purpose.
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U2 - 10.1529/biophysj.105.080069
DO - 10.1529/biophysj.105.080069
M3 - Article
C2 - 16513774
AN - SCOPUS:33646193716
SN - 0006-3495
VL - 90
SP - 3496
EP - 3510
JO - Biophysical journal
JF - Biophysical journal
IS - 10
ER -