Discovery of a novel response of ion channels to membrane potential, using molecular dynamics. More on this work here: https://doi.org/10.3389/fmolb.2020.00162
The public trial lecture presented by Mohammadreza Nematollahi on 8th of October 2014 at Norwegian University of Science and Technology. The theoretical models and the experimental progress of highly mismatched alloys, as well as their optoelectronic applications are covered.
1935 – Heil oscillator
1939 – klystron amplifier
1944 – Helix type TWT
In the early 1950s – low power output of linear beam tubes to high power levels
Finally invention of Magnetrons
Several devices were developed – two significant devices among them are
1) extended interaction klystron
2) Twystron hybrid amplifier
CYLINDRICAL
LINEAR
COAXIAL
VOLTAGE-TUNABLE
INVERTED COAXIAL
FREQUENCY-AGILE COAXIAL
Modeling and Optimization of Cold Crucible Furnaces for Melting MetalsFluxtrol Inc.
http://fluxtrol.com
Cold Crucible Furnaces (CCFs), widely used in multiple special applications of
melting metals, oxides, glasses and other materials [1], are essentially 3D devices and their modeling is a complicated task. Multiple studies of CCFs have been made for their
optimization, but their electrical efficiency is still low; for metals approximately 25-30% andeven lower. Fluxtrol, Inc., made an extensive study of electromagnetic processes of CCFs using computer simulation and laboratory tests. This study showed that electrical efficiency of CCFs may be strongly improved by means of optimal design of the whole system with use of magnetic flux controllers. Theoretical results had been confirmed by laboratory tests on mockups and by industrial tests with real melting processes. The presentation contains a description of the computer modeling procedure and major findings. They form a basis for optimal design of electromagnetic systems of CCFs.
The public trial lecture presented by Mohammadreza Nematollahi on 8th of October 2014 at Norwegian University of Science and Technology. The theoretical models and the experimental progress of highly mismatched alloys, as well as their optoelectronic applications are covered.
1935 – Heil oscillator
1939 – klystron amplifier
1944 – Helix type TWT
In the early 1950s – low power output of linear beam tubes to high power levels
Finally invention of Magnetrons
Several devices were developed – two significant devices among them are
1) extended interaction klystron
2) Twystron hybrid amplifier
CYLINDRICAL
LINEAR
COAXIAL
VOLTAGE-TUNABLE
INVERTED COAXIAL
FREQUENCY-AGILE COAXIAL
Modeling and Optimization of Cold Crucible Furnaces for Melting MetalsFluxtrol Inc.
http://fluxtrol.com
Cold Crucible Furnaces (CCFs), widely used in multiple special applications of
melting metals, oxides, glasses and other materials [1], are essentially 3D devices and their modeling is a complicated task. Multiple studies of CCFs have been made for their
optimization, but their electrical efficiency is still low; for metals approximately 25-30% andeven lower. Fluxtrol, Inc., made an extensive study of electromagnetic processes of CCFs using computer simulation and laboratory tests. This study showed that electrical efficiency of CCFs may be strongly improved by means of optimal design of the whole system with use of magnetic flux controllers. Theoretical results had been confirmed by laboratory tests on mockups and by industrial tests with real melting processes. The presentation contains a description of the computer modeling procedure and major findings. They form a basis for optimal design of electromagnetic systems of CCFs.
VITEEE 2015 is going to be conducted by CBSE during April 2015 to take admission into various Universities and Institutions. The Syllabus is based on CBSE 10+2 exam system covering class 11 & 12 syllabus.
Syllabus Contents:
1. Physics
2. Chemistry
3. Mathematics
www.entranceindia.com provides model papers for VITEEE and other medical and engineering entrance examinations in India. Our model papers are proved to be best where students could discover 12 questions matching in JEE Main 2014 examination. For more information please visit us today.
Carbon Nano tubes and its Applications in the Field of Electronics and Comput...ijsrd.com
With rapid advancement of technology and unlimited quest in the intricate fields of science led man to confront nano tubes. It consists of C60 Fullerenes with tube like structures capped at both ends delivering extraordinary mechanical and electrical properties. It is hard to stress as extremely low turn on for fields and has high current densities. It is also the best emission field emitter for future field emission displays. Can be extensively used for fuel cells and field emission display. We throw a light on the research on nano tubes and it's general applications. In this paper we are focusing and questioning the field of research to ponder for the betterment off life to nano tube.
Laterolog is an electrical sonde for measring the electrical resistivity of rocks with in a borehole.Normaly measure the resistivity of mud cake and invaded zone.
VITEEE 2015 is going to be conducted by CBSE during April 2015 to take admission into various Universities and Institutions. The Syllabus is based on CBSE 10+2 exam system covering class 11 & 12 syllabus.
Syllabus Contents:
1. Physics
2. Chemistry
3. Mathematics
www.entranceindia.com provides model papers for VITEEE and other medical and engineering entrance examinations in India. Our model papers are proved to be best where students could discover 12 questions matching in JEE Main 2014 examination. For more information please visit us today.
Trap and Transfer. Two-Step Hole Injection Across the Sb2S3/CuSCN Interface i...kamatlab
Trap and Transfer. Two-Step Hole Injection Across the Sb2S3/CuSCN Interface in Solid State Solar Cells. ACS Nano, 2013, ASAP.
DOI: 10.1021/nn403058f
In solid-state semiconductor-sensitized solar cells, commonly known as extremely thin absorber (ETA) or solid-state quantum dot sensitized solar cells (QDSCs), transfer of photogenerated holes from the absorber species to the p-type hole conductor plays a critical role in the charge separation process. Using Sb2S3 (absorber) and CuSCN (hole conductor), we have constructed ETA solar cells exhibiting a power conversion efficiency of 3.3%. The hole transfer from excited Sb2S3 into CuSCN, which limits the overall power conversion efficiency of these solar cells, is now independently studied using transient absorption spectroscopy. In the Sb2S3 absorber layer, photogenerated holes are rapidly localized on the sulfur atoms of the crystal lattice, forming a sulfide radical (S−•) species. This trapped hole is transferred from the Sb2S3 absorber to the CuSCN hole conductor with an exponential time constant of 1680 ps. This process was monitored through the spectroscopic signal seen for the S−• species in Sb2S3, providing direct evidence for the hole transfer dynamics in ETA solar cells. Elucidation of the hole transfer mechanism from Sb2S3 to CuSCN represents a significant step toward understanding charge separation in Sb2S3 solar cells, and provides insight into the design of new architectures for higher efficiency devices.
The effects of a displacive structural phase transition on sliding friction are in principle accessible to nanoscale tools such as atomic force microscopy, yet they are still surprisingly unexplored. We present model simulations demonstrating and clarifying the mechanism and potential impact of these effects. A structural order parameter inside the material will yield a contribution to stick slip friction that is nonmonotonic as temperature crosses the phase transition, peaking at the critical T c where critical fluctuations are strongest, and the sliding induced order-parameter local flips from one value to another more numerous. Accordingly, the friction below T c is larger when the order-parameter orientation is such that flips are more effectively triggered by the slider. The observability of these effects and their use for friction control are discussed, for future application to sliding on the surface of and ferro- or antiferrodistortive materials.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
VITEEE 2015 is going to be conducted by CBSE during April 2015 to take admission into various Universities and Institutions. The Syllabus is based on CBSE 10+2 exam system covering class 11 & 12 syllabus.
Syllabus Contents:
1. Physics
2. Chemistry
3. Mathematics
www.entranceindia.com provides model papers for VITEEE and other medical and engineering entrance examinations in India. Our model papers are proved to be best where students could discover 12 questions matching in JEE Main 2014 examination. For more information please visit us today.
Carbon Nano tubes and its Applications in the Field of Electronics and Comput...ijsrd.com
With rapid advancement of technology and unlimited quest in the intricate fields of science led man to confront nano tubes. It consists of C60 Fullerenes with tube like structures capped at both ends delivering extraordinary mechanical and electrical properties. It is hard to stress as extremely low turn on for fields and has high current densities. It is also the best emission field emitter for future field emission displays. Can be extensively used for fuel cells and field emission display. We throw a light on the research on nano tubes and it's general applications. In this paper we are focusing and questioning the field of research to ponder for the betterment off life to nano tube.
Laterolog is an electrical sonde for measring the electrical resistivity of rocks with in a borehole.Normaly measure the resistivity of mud cake and invaded zone.
VITEEE 2015 is going to be conducted by CBSE during April 2015 to take admission into various Universities and Institutions. The Syllabus is based on CBSE 10+2 exam system covering class 11 & 12 syllabus.
Syllabus Contents:
1. Physics
2. Chemistry
3. Mathematics
www.entranceindia.com provides model papers for VITEEE and other medical and engineering entrance examinations in India. Our model papers are proved to be best where students could discover 12 questions matching in JEE Main 2014 examination. For more information please visit us today.
Trap and Transfer. Two-Step Hole Injection Across the Sb2S3/CuSCN Interface i...kamatlab
Trap and Transfer. Two-Step Hole Injection Across the Sb2S3/CuSCN Interface in Solid State Solar Cells. ACS Nano, 2013, ASAP.
DOI: 10.1021/nn403058f
In solid-state semiconductor-sensitized solar cells, commonly known as extremely thin absorber (ETA) or solid-state quantum dot sensitized solar cells (QDSCs), transfer of photogenerated holes from the absorber species to the p-type hole conductor plays a critical role in the charge separation process. Using Sb2S3 (absorber) and CuSCN (hole conductor), we have constructed ETA solar cells exhibiting a power conversion efficiency of 3.3%. The hole transfer from excited Sb2S3 into CuSCN, which limits the overall power conversion efficiency of these solar cells, is now independently studied using transient absorption spectroscopy. In the Sb2S3 absorber layer, photogenerated holes are rapidly localized on the sulfur atoms of the crystal lattice, forming a sulfide radical (S−•) species. This trapped hole is transferred from the Sb2S3 absorber to the CuSCN hole conductor with an exponential time constant of 1680 ps. This process was monitored through the spectroscopic signal seen for the S−• species in Sb2S3, providing direct evidence for the hole transfer dynamics in ETA solar cells. Elucidation of the hole transfer mechanism from Sb2S3 to CuSCN represents a significant step toward understanding charge separation in Sb2S3 solar cells, and provides insight into the design of new architectures for higher efficiency devices.
The effects of a displacive structural phase transition on sliding friction are in principle accessible to nanoscale tools such as atomic force microscopy, yet they are still surprisingly unexplored. We present model simulations demonstrating and clarifying the mechanism and potential impact of these effects. A structural order parameter inside the material will yield a contribution to stick slip friction that is nonmonotonic as temperature crosses the phase transition, peaking at the critical T c where critical fluctuations are strongest, and the sliding induced order-parameter local flips from one value to another more numerous. Accordingly, the friction below T c is larger when the order-parameter orientation is such that flips are more effectively triggered by the slider. The observability of these effects and their use for friction control are discussed, for future application to sliding on the surface of and ferro- or antiferrodistortive materials.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Observation of Io’s Resurfacing via Plume Deposition Using Ground-based Adapt...Sérgio Sacani
Since volcanic activity was first discovered on Io from Voyager images in 1979, changes
on Io’s surface have been monitored from both spacecraft and ground-based telescopes.
Here, we present the highest spatial resolution images of Io ever obtained from a groundbased telescope. These images, acquired by the SHARK-VIS instrument on the Large
Binocular Telescope, show evidence of a major resurfacing event on Io’s trailing hemisphere. When compared to the most recent spacecraft images, the SHARK-VIS images
show that a plume deposit from a powerful eruption at Pillan Patera has covered part
of the long-lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth-based telescopes. The SHARK-VIS instrument ushers in a new era of high resolution imaging of Io’s surface using adaptive
optics at visible wavelengths.
Richard's aventures in two entangled wonderlandsRichard Gill
Since the loophole-free Bell experiments of 2020 and the Nobel prizes in physics of 2022, critics of Bell's work have retreated to the fortress of super-determinism. Now, super-determinism is a derogatory word - it just means "determinism". Palmer, Hance and Hossenfelder argue that quantum mechanics and determinism are not incompatible, using a sophisticated mathematical construction based on a subtle thinning of allowed states and measurements in quantum mechanics, such that what is left appears to make Bell's argument fail, without altering the empirical predictions of quantum mechanics. I think however that it is a smoke screen, and the slogan "lost in math" comes to my mind. I will discuss some other recent disproofs of Bell's theorem using the language of causality based on causal graphs. Causal thinking is also central to law and justice. I will mention surprising connections to my work on serial killer nurse cases, in particular the Dutch case of Lucia de Berk and the current UK case of Lucy Letby.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
THE IMPORTANCE OF MARTIAN ATMOSPHERE SAMPLE RETURN.Sérgio Sacani
The return of a sample of near-surface atmosphere from Mars would facilitate answers to several first-order science questions surrounding the formation and evolution of the planet. One of the important aspects of terrestrial planet formation in general is the role that primary atmospheres played in influencing the chemistry and structure of the planets and their antecedents. Studies of the martian atmosphere can be used to investigate the role of a primary atmosphere in its history. Atmosphere samples would also inform our understanding of the near-surface chemistry of the planet, and ultimately the prospects for life. High-precision isotopic analyses of constituent gases are needed to address these questions, requiring that the analyses are made on returned samples rather than in situ.
Earliest Galaxies in the JADES Origins Field: Luminosity Function and Cosmic ...Sérgio Sacani
We characterize the earliest galaxy population in the JADES Origins Field (JOF), the deepest
imaging field observed with JWST. We make use of the ancillary Hubble optical images (5 filters
spanning 0.4−0.9µm) and novel JWST images with 14 filters spanning 0.8−5µm, including 7 mediumband filters, and reaching total exposure times of up to 46 hours per filter. We combine all our data
at > 2.3µm to construct an ultradeep image, reaching as deep as ≈ 31.4 AB mag in the stack and
30.3-31.0 AB mag (5σ, r = 0.1” circular aperture) in individual filters. We measure photometric
redshifts and use robust selection criteria to identify a sample of eight galaxy candidates at redshifts
z = 11.5 − 15. These objects show compact half-light radii of R1/2 ∼ 50 − 200pc, stellar masses of
M⋆ ∼ 107−108M⊙, and star-formation rates of SFR ∼ 0.1−1 M⊙ yr−1
. Our search finds no candidates
at 15 < z < 20, placing upper limits at these redshifts. We develop a forward modeling approach to
infer the properties of the evolving luminosity function without binning in redshift or luminosity that
marginalizes over the photometric redshift uncertainty of our candidate galaxies and incorporates the
impact of non-detections. We find a z = 12 luminosity function in good agreement with prior results,
and that the luminosity function normalization and UV luminosity density decline by a factor of ∼ 2.5
from z = 12 to z = 14. We discuss the possible implications of our results in the context of theoretical
models for evolution of the dark matter halo mass function.
2. Voltage-gated potassium channels
THE most diverse group in the ion channel family
Functions in eukaryotic cells
- neural signaling
- cardiac rhythm
- potential drug target in cancer (Huang and Jan, JCB 2014)
e.g. restoration of the membrane potential after an action potential
Why voltage-gated K+ channels (Kv)?
12. The consensus model is applicable to some channels
Bignucolo and Bernèche (2020)
S3
S4
S1
S2
Kv1.2 Kv1.2/2.1
13. Bignucolo and Bernèche (2020)
S3
S4
S1
S2
Kv1.2 Kv1.2/2.1 KvAP
The consensus model is difficult to apply to other
channels like e.g. KvAP
14. Bignucolo and Bernèche (2020)
S3
S4
S1
S2
Kv1.2 Kv1.2/2.1 KvAP
A sliding of S4 would bring hydrophobic residues in
contact with hydrophilic species
15. What is the response of this family of channels to
membrane hyperpolarization?
1- Presentation of the double bilayer simulation system
2- A novel response of the Voltage-Sensor Domain to membrane hyperpolarization
3- Apply the model to the full-length structure
16. What is the response of this family of channels to
membrane hyperpolarization?
1- The double bilayer simulation system
2- A novel response of the Voltage-Sensor Domain to membrane hyperpolarization
3- Apply the model on the full-length structure
17. Usual bilayer: ion concentration gradient not feasible
‘Upper side’
‘Lower side’
“Usual” system:
periodic boundary conditions:
one solvent compartment
no ion differential
no membrane potential
20. Result: a biologically relevant system with
“inside” and “outside” compartments
Extracellular cell
compartment
Extracellular cell
compartment
Intracellular cell
compartment
21. One can generate a membrane potential (Vm)
Simply move a few ions “manually”
Vm = Vextracellular - Vintracellular
Black line : Vminit
Red line: Vmend
22. What is the response of this family of channels to
membrane hyperpolarization?
1- Presentation of the double bilayer simulation system
2- A novel response of the Voltage-Sensor Domain to
membrane hyperpolarization
3- Apply the model to the full-length structure
23. Constructed 65 such double bilayer systems and used
the electrostatic potential values for quality check
Deviation ≡ Vmend – Vminit
What is expected
deviation ~ 0 stable system
24. Four outliers charge transport !!
In four simulations
electric charge transport
25. The charge translocation depends on the initial Vm
R = 0.82
p < 0.001
Bignucolo and Bernèche (2020)
27. What happened in the four trajectories?
1) Rupture of the R133—D62 salt bridge
2) breakage of S4
Bignucolo and Bernèche (2020)
S4 Nter
S4 Cter
Gly134
Vm ~ 0
S4 straight
salt bridge formed
Vm << 0
S4 broken at G134
rupture of the salt bridge
28. What happened in the four trajectories?
1) Rupture of the R133—D62 salt bridge
2) breakage of S4
Bignucolo and Bernèche (2020)
S4 Nter
S4 Cter
Gly134
Vm ~ 0
S4 straight
salt bridge formed
Vm << 0
S4 broken at G134
rupture of the salt bridge
29. What happened in the four trajectories?
1) Rupture of the R133—D62 salt bridge
2) Breakage of S4
Bignucolo and Bernèche (2020)
S4 Nter
S4 Cter
Gly134
Vm ~ 0
S4 straight
salt bridge formed
Vm << 0
S4 broken at G134
rupture of the salt bridge
30. What happened in the four trajectories?
1) Rupture of the R133—D62 salt bridge
2) Breakage of S4
3) This specific sequence: only prokaryotes and archaea
Bignucolo and Bernèche (2020)
S4 Nter
S4 Cter
Gly134
Vm ~ 0
S4 straight
salt bridge formed
Vm << 0
S4 broken at G134
rupture of the salt bridge
31. Co-occurrence of the salt bridge rupture and
the S4 breakage ? upon hyperpolarization
S4 bending angle time
evolution of trajectories in
which the distance between
Asp62 and Arg133 remained
stable at ∼ 2Å (nVSD = 126).
S4 bending angle time
evolution of the four
trajectories harboring a charge
translocation
S1
S2
D62
R133
S3
S4
Salt bridge distance of the four trajectories
harboring a charge translocation
S4 bending angle of the four
trajectories harboring a charge
translocation
32. Normalization to the time of the salt bridge
rupture what happens to S4?
S4 bending angle time
evolution of trajectories in
which the distance between
Asp62 and Arg133 remained
stable at ∼ 2Å (nVSD = 126).
S4 bending angle time
evolution of the four
trajectories harboring a charge
translocation
S1
S2
D62
R133
S3
S4
Salt bridge distance of the four trajectories
harboring a charge translocation
S4 bending angle of the four
trajectories harboring a charge
translocation
33. The S4 breakage and the rupture of the salt
bridge occur simultaneously
S4 bending angle time
evolution of trajectories in
which the distance between
Asp62 and Arg133 remained
stable at ∼ 2Å (nVSD = 126).
S4 bending angle time
evolution of the four
trajectories harboring a charge
translocation
S1
S2
D62
R133
S3
S4
The time points of the salt
bridge rupture and initiation
of S4 bending superpose
exactly
34. Co-occurrence of the salt bridge rupture and
the S4 breakage upon hyperpolarization
Bignucolo and Bernèche (2020)
S4 bending angle time
evolution of trajectories in
which the distance between
Asp62 and Arg133 remained
stable at ∼ 2Å (nVSD = 122).
S1
S2
D62
R133
S3
S4 C-Ter
35. Co-occurrence of the salt bridge rupture and
the S4 breakage upon hyperpolarization
Bignucolo and Bernèche (2020)
36. Co-occurrence of the salt bridge rupture and
the S4 breakage upon hyperpolarization
Bignucolo and Bernèche (2020)
37. Co-occurrence of the salt bridge rupture and
the S4 breakage upon hyperpolarization
Displaced ions to
generate a positive
membrane potential
38. Restoration of the salt bridge and the S4
breakage upon depolarization
Restoration of the
salt bridge
39. The bending of S4 follows a similar trend
Restoration of the
salt bridge
40. What is the response of this family of channels to
membrane hyperpolarization?
1- The double bilayer simulation system
2- A novel response of the Voltage-Sensor Domain to membrane hyperpolarization
3- Apply the model to the full-length structure
Tao and MacKinnon (2019)
41. Dec. 2019: Full-length structure of KvAP
Structure published by Tao and MacKinnon (2019) inserted in a lipid bilayer
Brown spheres:
Phosphorous atoms
Each monomer a different colour:
blue, red, orange, grey
42. Details of the active state (at Vm = 0)
S1
S2
S3 S4 S5 pore helix and S6
Selectivity filter
Voltage-sensor Pore domain Voltage-sensor
43. G134 Ca
Pull force to induce the known bending of S4
Apply the model on the cryo-EM structure
1) Pull force S4 bending after ~ 23 ns
2) 17 double bilayer systems, exposed to various Vm values
44. Apply the model on the cryo-EM structure
1) Pull force S4 bending after ~ 23 ns
2) 17 double bilayer systems, exposed to various Vm values
48. Apply the model on the cryo-EM structure
1) Pull force S4 bending after ~ 23 ns
2) 17 double bilayer systems, 136 VSDs exposed to various Vm
Vm << 0 --> S4 Broken, n = 19
Vm ~ 0 --> S4 Straight, n = 33
Discard the intermediate cases
for statistical analysis
49. How does the breakage of S4 affects the pore domain?
we observe the S5 helix orientation
Bignucolo and Bernèche (2020)
S5
S4
50. How does the breakage of S4 affects the pore domain?
Effect of the pull force on S4 C-ter
S5
S4
62. Relevance:
- First complete description of the interactions from S4 to the pore helix
in a Kv channel
- The “consensus” model should be extended to take this response into
account
- Other points, not shown here
- sequence unique to prokaryotes
- solution to the avidin accessibility experiment paradox
Bignucolo and Bernèche (2020)
63. Thanks!
This meeting:
Molecular Modelling Group
Vincent Zoete, Olivier Michielin
Ute Roehrig
and Team
The paper:
Simon Bernèche, Swiss Institute of Bioinformatics
Annaïse Jauch, University of Basel
Niklaus Johner, University of Basel
Stephan Kellenberger, University of Lausanne
and the reviewers of the journal
64.
65. What is really new?
Shenkarev et. al (2010) NMR investigation detects a loss of helicity near Gly134
Hints about a possible breakage of S4
No mention of the salt bridge
No membrane potential
Butterwick and Mackinnon (2010) The NMR structure of the VSD == 20 conformations
Three conformations harboured a bended S4 helix
Not commented in the article
Freites and Tobias (2015) Very long MD simulation with membrane potential
Detection of the salt-bridge rupture response to Vm
No mention of the S4 breakage
66. This is new:
The two conformational changes occur simultaneously and constitute
together the response of the VSD to the hyperpolarization
Shenkarev et. al (2010) NMR investigation detects a loss of helicity near Gly134
Hints about a possible breakage of S4
No mention of the salt bridge
No membrane potential
Butterwick and Mackinnon (2010) The NMR structure of the VSD == 20 conformations
Three conformations harboured a bended S4 helix
Not commented in the article
Freites and Tobias (2015) Very long MD simulation with membrane potential
Detection of the salt-bridge rupture response to Vm
No mention of the S4 breakage