scholarly journals Exploring the Complex Dynamics of an Ion Channel Voltage Sensor Domain via Computation

2017 ◽  
Author(s):  
Lucie Delemotte ◽  
Marina A. Kasimova ◽  
Daniel Sigg ◽  
Michael L. Klein ◽  
Vincenzo Carnevale ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Complex Dynamics ◽  
Critical Role ◽  
Alpha Helix ◽  
Md Simulations ◽  
Voltage Sensor ◽  
Gating Currents ◽  
Excitable Membranes ◽  
Voltage Gated Ion Channels ◽  
Voltage Sensor Domain

AbstractVoltage-gated ion channels are ubiquitous proteins that orchestrate electrical signaling across excitable membranes. Key to their function is activation of the voltage sensor domain (VSD), a transmembrane four alpha-helix bundle that triggers channel opening. Modeling of currents from electrophysiology experiments yields a set of kinetic parameters for a given channel, but no direct molecular insight. Here we use molecular dynamics (MD) simulations to determine the free energy landscape of VSD activation and to, ultimately, predict the time evolution of the resulting gating currents. Our study provides the long-sought-for bridge between electrophysiology and microscopic molecular dynamics and confirms, as already suggested on the basis of experiments, that rate-limiting barriers play a critical role in activation kinetics.

scholarly journals Mode shift of the voltage sensors in Shaker K+ channels is caused by energetic coupling to the pore domain

2011 ◽  
Vol 137 (5) ◽  
pp. 455-472 ◽  
Author(s):  
Georges A. Haddad ◽  
Rikard Blunck
Keyword(s):  
Conformational Change ◽  
Mechanical Load ◽  
Voltage Sensor ◽  
Charge Movement ◽  
Gating Currents ◽  
Mode Shift ◽  
Voltage Sensors ◽  
Pore Opening ◽  
Voltage Gated Ion Channels ◽  
Pore Domain

The voltage sensors of voltage-gated ion channels undergo a conformational change upon depolarization of the membrane that leads to pore opening. This conformational change can be measured as gating currents and is thought to be transferred to the pore domain via an annealing of the covalent link between voltage sensor and pore (S4-S5 linker) and the C terminus of the pore domain (S6). Upon prolonged depolarizations, the voltage dependence of the charge movement shifts to more hyperpolarized potentials. This mode shift had been linked to C-type inactivation but has recently been suggested to be caused by a relaxation of the voltage sensor itself. In this study, we identified two ShakerIR mutations in the S4-S5 linker (I384N) and S6 (F484G) that, when mutated, completely uncouple voltage sensor movement from pore opening. Using these mutants, we show that the pore transfers energy onto the voltage sensor and that uncoupling the pore from the voltage sensor leads the voltage sensors to be activated at more negative potentials. This uncoupling also eliminates the mode shift occurring during prolonged depolarizations, indicating that the pore influences entry into the mode shift. Using voltage-clamp fluorometry, we identified that the slow conformational change of the S4 previously correlated with the mode shift disappears when uncoupling the pore. The effects can be explained by a mechanical load that is imposed upon the voltage sensors by the pore domain and allosterically modulates its conformation. Mode shift is caused by the stabilization of the open state but leads to a conformational change in the voltage sensor.

scholarly journals The Conformational Transition of Kv1.2 Voltage Sensor Domain from Molecular Dynamics Simulations

2011 ◽  
Vol 100 (3) ◽  
pp. 284a-285a
Author(s):  
Luca Maragliano ◽  
Fatemeh Khalili-Araghi ◽  
Emad Tajkhorshid ◽  
Klaus Schulten ◽  
Benoit Roux
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Conformational Transition ◽  
Voltage Sensor ◽  
Dynamics Simulations ◽  
Voltage Sensor Domain

scholarly journals Mechanisms in Carbon Nanotube Growth: Modelling and Molecular Dynamics Simulations

2021 ◽  
Author(s):  
◽  
Dmitri Schebarchov
Keyword(s):  
Molecular Dynamics ◽  
Carbon Nanotube ◽  
Supported Catalysts ◽  
Critical Role ◽  
Chemical Vapour ◽  
Catalyst Particle ◽  
Md Simulations ◽  
Capillary Absorption ◽  
Supported Nickel Catalyst ◽  
Lift Off

<p>A selection of nanoscale processes is studied theoretically, with the aim of identifying themechanisms that could lead to selective carbon nanotube (CNT) growth. Only mechanisms relevant to catalytic chemical vapour deposition (CVD) are considered. The selected processes are analysed with classical molecular dynamics (MD) simulations and continuum modelling. The melting and pre-melting behaviour of supported nickel catalyst particles is investigated. Favourable epitaxy between a nanoparticle and the substrate is shown to significantly raise themelting point of the particle. It is also demonstrated that substrate binding can induce solid-solid transformations, whilst the epitaxy may even determine the orientation of individual crystal planes in supported catalysts. These findings suggest that the substrate crystal structure alone can potentially be used to manipulate the properties of catalyst particles and, hence, influence the structure of CNTs. The first attempt at modelling catalyst dewetting, a process where the catalyst unbinds from the inner walls of a nucleating nanotube, is presented. It is argued that understanding this process and gaining control over itmay lead to better selectivity in CNT growth. Two mutually exclusive dewetting mechanisms, namely cap lift-off and capillary withdrawal, are identified and then modelled as elastocapillary phenomena. The modelling yields an upper bound on the diameter of CNTs that can stem from a catalyst particle of a given size. It is also demonstrated that cap lift-off is sensitive to cap topology, suggesting that it may be possible to link catalyst characteristics to the structural properties of nucleating CNTs. However, a clear link to the chiral vector remains elusive. It is shown that particle size, as well as binding affinity, plays a critical role in capillary absorption and withdrawal of catalyst nanoparticles. This size dependence is explored in detail, revealing interesting ramifications to the statics and dynamics of capillary-driven flows at the nanoscale. The findings bear significant implications for our understanding of CNT growth from catalyst particles, whilst also suggesting new nanofluidic applications and methods for fabricating composite metal-CNT materials.</p>

scholarly journals Mechanisms in Carbon Nanotube Growth: Modelling and Molecular Dynamics Simulations

2021 ◽  
Author(s):  
◽  
Dmitri Schebarchov
Keyword(s):  
Molecular Dynamics ◽  
Carbon Nanotube ◽  
Supported Catalysts ◽  
Critical Role ◽  
Chemical Vapour ◽  
Catalyst Particle ◽  
Md Simulations ◽  
Capillary Absorption ◽  
Supported Nickel Catalyst ◽  
Lift Off

<p><b>A selection of nanoscale processes is studied theoretically, with the aim of identifying themechanisms that could lead to selective carbon nanotube (CNT) growth. Only mechanisms relevant to catalytic chemical vapour deposition (CVD) are considered. The selected processes are analysed with classical molecular dynamics (MD) simulations and continuum modelling.</b></p> <p>The melting and pre-melting behaviour of supported nickel catalyst particles is investigated. Favourable epitaxy between a nanoparticle and the substrate is shown to significantly raise themelting point of the particle. It is also demonstrated that substrate binding can induce solid-solid transformations, whilst the epitaxy may even determine the orientation of individual crystal planes in supported catalysts. These findings suggest that the substrate crystal structure alone can potentially be used to manipulate the properties of catalyst particles and, hence, influence the structure of CNTs.</p> <p>The first attempt at modelling catalyst dewetting, a process where the catalyst unbinds from the inner walls of a nucleating nanotube, is presented. It is argued that understanding this process and gaining control over itmay lead to better selectivity in CNT growth. Two mutually exclusive dewetting mechanisms, namely cap lift-off and capillary withdrawal, are identified and then modelled as elastocapillary phenomena. The modelling yields an upper bound on the diameter of CNTs that can stem from a catalyst particle of a given size. It is also demonstrated that cap lift-off is sensitive to cap topology, suggesting that it may be possible to link catalyst characteristics to the structural properties of nucleating CNTs. However, a clear link to the chiral vector remains elusive.</p> <p>It is shown that particle size, as well as binding affinity, plays a critical role in capillary absorption and withdrawal of catalyst nanoparticles. This size dependence is explored in detail, revealing interesting ramifications to the statics and dynamics of capillary-driven flows at the nanoscale. The findings bear significant implications for our understanding of CNT growth from catalyst particles, whilst also suggesting new nanofluidic applications and methods for fabricating composite metal-CNT materials.</p>

scholarly journals Mechanisms in Carbon Nanotube Growth: Modelling and Molecular Dynamics Simulations

2021 ◽  
Author(s):  
◽  
Dmitri Schebarchov
Keyword(s):  
Molecular Dynamics ◽  
Carbon Nanotube ◽  
Supported Catalysts ◽  
Critical Role ◽  
Chemical Vapour ◽  
Catalyst Particle ◽  
Md Simulations ◽  
Capillary Absorption ◽  
Supported Nickel Catalyst ◽  
Lift Off

<p>A selection of nanoscale processes is studied theoretically, with the aim of identifying themechanisms that could lead to selective carbon nanotube (CNT) growth. Only mechanisms relevant to catalytic chemical vapour deposition (CVD) are considered. The selected processes are analysed with classical molecular dynamics (MD) simulations and continuum modelling. The melting and pre-melting behaviour of supported nickel catalyst particles is investigated. Favourable epitaxy between a nanoparticle and the substrate is shown to significantly raise themelting point of the particle. It is also demonstrated that substrate binding can induce solid-solid transformations, whilst the epitaxy may even determine the orientation of individual crystal planes in supported catalysts. These findings suggest that the substrate crystal structure alone can potentially be used to manipulate the properties of catalyst particles and, hence, influence the structure of CNTs. The first attempt at modelling catalyst dewetting, a process where the catalyst unbinds from the inner walls of a nucleating nanotube, is presented. It is argued that understanding this process and gaining control over itmay lead to better selectivity in CNT growth. Two mutually exclusive dewetting mechanisms, namely cap lift-off and capillary withdrawal, are identified and then modelled as elastocapillary phenomena. The modelling yields an upper bound on the diameter of CNTs that can stem from a catalyst particle of a given size. It is also demonstrated that cap lift-off is sensitive to cap topology, suggesting that it may be possible to link catalyst characteristics to the structural properties of nucleating CNTs. However, a clear link to the chiral vector remains elusive. It is shown that particle size, as well as binding affinity, plays a critical role in capillary absorption and withdrawal of catalyst nanoparticles. This size dependence is explored in detail, revealing interesting ramifications to the statics and dynamics of capillary-driven flows at the nanoscale. The findings bear significant implications for our understanding of CNT growth from catalyst particles, whilst also suggesting new nanofluidic applications and methods for fabricating composite metal-CNT materials.</p>

scholarly journals Exploring Conformational Transition of 2019 Novel Coronavirus Spike Glycoprotein Between Its Closed and Open States Using Molecular Dynamics Simulations

2020 ◽  
Author(s):  
Mert Gur ◽  
Elhan Taka ◽  
Sema Zeynep Yilmaz ◽  
Ceren Kilinc ◽  
Umut Aktas ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Host Cell ◽  
Crystal Structures ◽  
Critical Role ◽  
Minimum Energy ◽  
Md Simulations ◽  
Host Cells ◽  
Spike Protein ◽  
Novel Coronavirus ◽  
Open States

ABSTRACTSince its first recorded appearance in December 2019, a novel coronavirus (SARS-CoV-2) causing the disease COVID-19 has resulted in more than 2,000,000 infections and 128,000 deaths. Currently there is no proven treatment for COVID-19 and there is an urgent need for the development of vaccines and therapeutics. Coronavirus spike glycoproteins play a critical role in coronavirus entry into the host cells, as they provide host cell recognition and membrane fusion between virus and host cell. Thus, they emerged as popular and promising drug targets. Crystal structures of spike protein in its closed and open states were resolved very recently in March 2020. These structures comprise 77% of the sequence and provide almost the complete protein structure. Based on down and up positions of receptor binding domain (RBD), spike protein can be in a receptor inaccessible closed or receptor accessible open state, respectively. Starting from closed and open state crystal structures, and also 16 intermediate conformations, an extensive set of all-atom molecular dynamics (MD) simulations in the presence of explicit water and ions were performed. Simulations show that in its down position, RBD has significantly lower mobility compared to its up position; probably caused by the 6 interdomain salt bridges of RBD in down position compared to 3 in up position. Free energy landscapes based on MD simulations revealed a semi-open state located between closed and open states. Minimum energy pathway between down and up positions comprised a gradual salt bridge switching mechanism. Furthermore, although significantly lower than open state, ACE2 binding surface of RBD contained a partial solvent accessibility in its closed state.

scholarly journals Mechanisms in Carbon Nanotube Growth: Modelling and Molecular Dynamics Simulations

2021 ◽  
Author(s):  
◽  
Dmitri Schebarchov
Keyword(s):  
Molecular Dynamics ◽  
Carbon Nanotube ◽  
Supported Catalysts ◽  
Critical Role ◽  
Chemical Vapour ◽  
Catalyst Particle ◽  
Md Simulations ◽  
Capillary Absorption ◽  
Supported Nickel Catalyst ◽  
Lift Off

<p><b>A selection of nanoscale processes is studied theoretically, with the aim of identifying themechanisms that could lead to selective carbon nanotube (CNT) growth. Only mechanisms relevant to catalytic chemical vapour deposition (CVD) are considered. The selected processes are analysed with classical molecular dynamics (MD) simulations and continuum modelling.</b></p> <p>The melting and pre-melting behaviour of supported nickel catalyst particles is investigated. Favourable epitaxy between a nanoparticle and the substrate is shown to significantly raise themelting point of the particle. It is also demonstrated that substrate binding can induce solid-solid transformations, whilst the epitaxy may even determine the orientation of individual crystal planes in supported catalysts. These findings suggest that the substrate crystal structure alone can potentially be used to manipulate the properties of catalyst particles and, hence, influence the structure of CNTs.</p> <p>The first attempt at modelling catalyst dewetting, a process where the catalyst unbinds from the inner walls of a nucleating nanotube, is presented. It is argued that understanding this process and gaining control over itmay lead to better selectivity in CNT growth. Two mutually exclusive dewetting mechanisms, namely cap lift-off and capillary withdrawal, are identified and then modelled as elastocapillary phenomena. The modelling yields an upper bound on the diameter of CNTs that can stem from a catalyst particle of a given size. It is also demonstrated that cap lift-off is sensitive to cap topology, suggesting that it may be possible to link catalyst characteristics to the structural properties of nucleating CNTs. However, a clear link to the chiral vector remains elusive.</p> <p>It is shown that particle size, as well as binding affinity, plays a critical role in capillary absorption and withdrawal of catalyst nanoparticles. This size dependence is explored in detail, revealing interesting ramifications to the statics and dynamics of capillary-driven flows at the nanoscale. The findings bear significant implications for our understanding of CNT growth from catalyst particles, whilst also suggesting new nanofluidic applications and methods for fabricating composite metal-CNT materials.</p>

scholarly journals An emerging consensus on voltage-dependent gating from computational modeling and molecular dynamics simulations

2012 ◽  
Vol 140 (6) ◽  
pp. 587-594 ◽  
Author(s):  
Ernesto Vargas ◽  
Vladimir Yarov-Yarovoy ◽  
Fatemeh Khalili-Araghi ◽  
William A. Catterall ◽  
Michael L. Klein ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Computational Modeling ◽  
Md Simulations ◽  
Missing Information ◽  
Voltage Gated ◽  
Voltage Dependent ◽  
Voltage Gated Channels ◽  
Voltage Gated Ion Channels ◽  
Dynamics Simulations ◽  
Resolution Structure

Developing an understanding of the mechanism of voltage-gated ion channels in molecular terms requires knowledge of the structure of the active and resting conformations. Although the active-state conformation is known from x-ray structures, an atomic resolution structure of a voltage-dependent ion channel in the resting state is not currently available. This has motivated various efforts at using computational modeling methods and molecular dynamics (MD) simulations to provide the missing information. A comparison of recent computational results reveals an emerging consensus on voltage-dependent gating from computational modeling and MD simulations. This progress is highlighted in the broad context of preexisting work about voltage-gated channels.

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