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Masahiro Kinoshita - One of the best experts on this subject based on the ideXlab platform.
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physics of multidrug efflux through a Biomolecular Complex
Biophysical Journal, 2014Co-Authors: Hirokazu Mishima, Hiraku Oshima, Satoshi Yasuda, Kenichi Amano, Masahiro KinoshitaAbstract:Insertion and release of a solute into and from a vessel comprising biopolymers is a fundamental function. A typical example is found in a multidrug efflux transporter. “Multidrug efflux” signifies that solutes such as drug molecules with diverse properties can be handled. In earlier works, we showed that the spatial distribution of the solute-vessel potential of mean force (PMF) induced by the solvent plays imperative roles in the insertion/release process. The PMF can be decomposed into the energetic and entropic components. The entropic component, which originates from the translational displacement of solvent molecules, is rather insensitive to the solute-solvent and vessel inner surface-solvent affinities. This feature is not shared with the energetic component. When the vessel inner surface is neither solvophobic nor solvophilic, the solvents within the vessel cavity and in the bulk offer almost the same environment to any solute, and the energetic component becomes much smaller than the entropic component. Our idea is that the multidrug efflux can be realized if the insertion/release process is accomplished by the entropic component. However, we have recently argued that the entropic release is not feasible as long as the vessel geometry is fixed. Here we consider a model of TolC, a cylindrical vessel possessing an entrance at one end and an exit at the other end for the solute. The spatial distribution of the PMF is calculated by employing the three-dimensional integral equation theory with rigid-body models whose behavior is purely entropic in origin. We show that the entropically inserted solute can be released by a continuous variation of the vessel geometry which forms a time-dependent entropic force continuing to accelerate the solute motion to the exit. Solutes with a wide range of sizes are entropically released using the same vessel-geometry variation.
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on the physics of multidrug efflux through a Biomolecular Complex
Journal of Chemical Physics, 2013Co-Authors: Hirokazu Mishima, Hiraku Oshima, Satoshi Yasuda, Kenichi Amano, Masahiro KinoshitaAbstract:Insertion and release of a solute into and from a vessel comprising biopolymers is a fundamental function in a biological system. A typical example is found in a multidrug efflux transporter. “Multidrug efflux” signifies that solutes such as drug molecules with diverse properties can be handled. In our view, the mechanism of the multidrug efflux is not chemically specific but rather has to be based on a physical factor. In earlier works, we showed that the spatial distribution of the solute-vessel potential of mean force (PMF) induced by the solvent plays imperative roles in the insertion/release process. The PMF can be decomposed into the energetic and entropic components. The entropic component, which originates from the translational displacement of solvent molecules, is rather insensitive to the solute-solvent and vessel inner surface-solvent affinities. This feature is not shared with the energetic component. When the vessel inner surface is neither solvophobic nor solvophilic, the solvents within the vessel cavity and in the bulk offer almost the same environment to any solute with solvophobicity or solvophilicity, and the energetic component becomes much smaller than the entropic component (i.e., the latter predominates over the former). Our idea is that the multidrug efflux can be realized if the insertion/release process is accomplished by the entropic component exhibiting the insensitivity to the solute properties. However, we have recently argued that the entropic release of the solute is not feasible as long as the vessel geometry is fixed. Here we consider a model of TolC, a cylindrical vessel possessing an entrance at one end and an exit at the other end for the solute. The spatial distribution of the PMF is calculated by employing the three-dimensional integral equation theory with rigid-body models in which the constituents interact only through hard-body potentials. Since the behavior of these models is purely entropic in origin, our analysis is focused on the entropic component. We show that the entropically inserted solute can be released by a continuous variation of the vessel geometry which forms a time-dependent entropic force continuing to accelerate the solute motion to the exit. Solutes with a wide range of sizes are entropically released using the same vessel-geometry variation. The results obtained are fairly general and also applicable to the efflux pump protein AcrB and ATP-binding cassette transporter.
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potential of mean force between a large solute and a Biomolecular Complex a model analysis on protein flux through chaperonin system
Journal of Chemical Physics, 2011Co-Authors: Kenich Amano, Hiraku Oshima, Masahiro KinoshitaAbstract:Insertion of a large solute into an even larger vessel comprising biopolymers followed by release of the same solute from it is one of the important functions sustaining life. As a typical example, an unfolded protein is inserted into a chaperonin from bulk aqueous solution, a cochaperonin acting as a lid is attached to the chaperonin rim and the protein folds into its native structure within the closed cavity, the cochaperonin is detached after the folding is finished, and the folded protein is released back to the bulk solution. On the basis of the experimental observations manifesting that the basic aspects of the protein flux through the chaperonin system is independent of the chaperonin, cochaperonin, and protein species, we adopt a simple model system with which we can cover the whole cycle of the protein flux. We calculate the spatial distribution of the solvent-mediated potential of mean force (PMF) between a spherical solute and a cylindrical vessel or vessel/lid Complex. The calculation is performed using the three-dimensional integral equation theory, and the PMF is decomposed into energetic and entropic components. We argue that an unfolded protein with a larger excluded volume (EV) and weak hydrophobicity is entropically inserted into the chaperonin cavity and constrained within a small space almost in its center. The switch from insertion to release is achieved by decreasing the EV and turning the protein surface hydrophilic in the folding process. For this release, in which the energetic component is a requisite, the feature that the chaperonin inner surface in the absence of the cochaperonin is not hydrophilic plays essential roles. On the other hand, the inner surface of the chaperonin/cochaperonin Complex is hydrophilic, and the protein is energetically repelled from it: The protein remains constrained within the small space mentioned above without contacting the inner surface for correct folding. The structural and inner-surface properties of the chaperonin or Complex are controlled by the adenosine triphosphate (ATP) binding to the chaperonin, hydrolysis of ATP into adenosine diphosphate (ADP) and Pi, and dissociation of ADP and Pi. The function of the chaperonin system is exhibited by synchronizing the chemical cycle of ATP hydrolysis with hydration properties of a protein in the water confined on the scale of a nanometer which are substantially different from those in the bulk water.
Heng Kwong Tsao - One of the best experts on this subject based on the ideXlab platform.
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forced dissociation of a Biomolecular Complex under periodic and correlated random forcing
Journal of Chemical Physics, 2008Co-Authors: Han Jou Lin, Yu Jane Sheng, Hsuanyi Chen, Heng Kwong TsaoAbstract:The dissociation of a Biomolecular Complex under the action of periodic and correlated random forcing is studied theoretically. The former is characterized by the period τp and the latter by the correlation time τr. The rupture rates are calculated by overdamped Langevin dynamics and three distinct regimes are identified for both cases by comparison to local relaxation time τR and bond lifetime ⟨T⟩. For periodic forcing, the adiabatic approximation cannot be applied in the regime τp⪡τR and the bond lifetime is determined by the average pulling. As τR⪡τp⪡⟨T⟩, the rupture rate is enhanced by periodic forcing but is τp independent. Analytical expressions are obtained for small and large force amplitudes. As ⟨T⟩⪡τp, the rupture rate depends on the phase lag and the process behaves like it is under constant force or loading rate. The result of correlated random forcing is similar to that of periodic forcing. Since the fluctuating forces greater than the average force ⟨F⟩ contribute more than the fluctuating fo...
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bell s expression and the generalized garg form for forced dissociation of a Biomolecular Complex
Physical Review Letters, 2007Co-Authors: H Lin, Yu Jane Sheng, Hsuanyi Chen, Heng Kwong TsaoAbstract:The dissociation of a Biomolecular Complex under the action of constant force, constant loading rate, and periodic force is studied theoretically. We show that the celebrated Bell expression provides a good approximation for the bond dissociation rate when F/F(c)<<1, where F(c) is the maxima slope of the binding potential along the reaction coordinate. When 1-F/F(c) <<1 the dissociation rate is better described by a generalized Garg form in which the potential derivative is expanded near F(c). We also show that a constant-force experiment is suitable for extracting the activation energy of the bond, a constant loading experiment is suitable to extract F(c), while time-periodic force can be applied to extract both bond dissociation rates at zero force and F(c).
Hiraku Oshima - One of the best experts on this subject based on the ideXlab platform.
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physics of multidrug efflux through a Biomolecular Complex
Biophysical Journal, 2014Co-Authors: Hirokazu Mishima, Hiraku Oshima, Satoshi Yasuda, Kenichi Amano, Masahiro KinoshitaAbstract:Insertion and release of a solute into and from a vessel comprising biopolymers is a fundamental function. A typical example is found in a multidrug efflux transporter. “Multidrug efflux” signifies that solutes such as drug molecules with diverse properties can be handled. In earlier works, we showed that the spatial distribution of the solute-vessel potential of mean force (PMF) induced by the solvent plays imperative roles in the insertion/release process. The PMF can be decomposed into the energetic and entropic components. The entropic component, which originates from the translational displacement of solvent molecules, is rather insensitive to the solute-solvent and vessel inner surface-solvent affinities. This feature is not shared with the energetic component. When the vessel inner surface is neither solvophobic nor solvophilic, the solvents within the vessel cavity and in the bulk offer almost the same environment to any solute, and the energetic component becomes much smaller than the entropic component. Our idea is that the multidrug efflux can be realized if the insertion/release process is accomplished by the entropic component. However, we have recently argued that the entropic release is not feasible as long as the vessel geometry is fixed. Here we consider a model of TolC, a cylindrical vessel possessing an entrance at one end and an exit at the other end for the solute. The spatial distribution of the PMF is calculated by employing the three-dimensional integral equation theory with rigid-body models whose behavior is purely entropic in origin. We show that the entropically inserted solute can be released by a continuous variation of the vessel geometry which forms a time-dependent entropic force continuing to accelerate the solute motion to the exit. Solutes with a wide range of sizes are entropically released using the same vessel-geometry variation.
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on the physics of multidrug efflux through a Biomolecular Complex
Journal of Chemical Physics, 2013Co-Authors: Hirokazu Mishima, Hiraku Oshima, Satoshi Yasuda, Kenichi Amano, Masahiro KinoshitaAbstract:Insertion and release of a solute into and from a vessel comprising biopolymers is a fundamental function in a biological system. A typical example is found in a multidrug efflux transporter. “Multidrug efflux” signifies that solutes such as drug molecules with diverse properties can be handled. In our view, the mechanism of the multidrug efflux is not chemically specific but rather has to be based on a physical factor. In earlier works, we showed that the spatial distribution of the solute-vessel potential of mean force (PMF) induced by the solvent plays imperative roles in the insertion/release process. The PMF can be decomposed into the energetic and entropic components. The entropic component, which originates from the translational displacement of solvent molecules, is rather insensitive to the solute-solvent and vessel inner surface-solvent affinities. This feature is not shared with the energetic component. When the vessel inner surface is neither solvophobic nor solvophilic, the solvents within the vessel cavity and in the bulk offer almost the same environment to any solute with solvophobicity or solvophilicity, and the energetic component becomes much smaller than the entropic component (i.e., the latter predominates over the former). Our idea is that the multidrug efflux can be realized if the insertion/release process is accomplished by the entropic component exhibiting the insensitivity to the solute properties. However, we have recently argued that the entropic release of the solute is not feasible as long as the vessel geometry is fixed. Here we consider a model of TolC, a cylindrical vessel possessing an entrance at one end and an exit at the other end for the solute. The spatial distribution of the PMF is calculated by employing the three-dimensional integral equation theory with rigid-body models in which the constituents interact only through hard-body potentials. Since the behavior of these models is purely entropic in origin, our analysis is focused on the entropic component. We show that the entropically inserted solute can be released by a continuous variation of the vessel geometry which forms a time-dependent entropic force continuing to accelerate the solute motion to the exit. Solutes with a wide range of sizes are entropically released using the same vessel-geometry variation. The results obtained are fairly general and also applicable to the efflux pump protein AcrB and ATP-binding cassette transporter.
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potential of mean force between a large solute and a Biomolecular Complex a model analysis on protein flux through chaperonin system
Journal of Chemical Physics, 2011Co-Authors: Kenich Amano, Hiraku Oshima, Masahiro KinoshitaAbstract:Insertion of a large solute into an even larger vessel comprising biopolymers followed by release of the same solute from it is one of the important functions sustaining life. As a typical example, an unfolded protein is inserted into a chaperonin from bulk aqueous solution, a cochaperonin acting as a lid is attached to the chaperonin rim and the protein folds into its native structure within the closed cavity, the cochaperonin is detached after the folding is finished, and the folded protein is released back to the bulk solution. On the basis of the experimental observations manifesting that the basic aspects of the protein flux through the chaperonin system is independent of the chaperonin, cochaperonin, and protein species, we adopt a simple model system with which we can cover the whole cycle of the protein flux. We calculate the spatial distribution of the solvent-mediated potential of mean force (PMF) between a spherical solute and a cylindrical vessel or vessel/lid Complex. The calculation is performed using the three-dimensional integral equation theory, and the PMF is decomposed into energetic and entropic components. We argue that an unfolded protein with a larger excluded volume (EV) and weak hydrophobicity is entropically inserted into the chaperonin cavity and constrained within a small space almost in its center. The switch from insertion to release is achieved by decreasing the EV and turning the protein surface hydrophilic in the folding process. For this release, in which the energetic component is a requisite, the feature that the chaperonin inner surface in the absence of the cochaperonin is not hydrophilic plays essential roles. On the other hand, the inner surface of the chaperonin/cochaperonin Complex is hydrophilic, and the protein is energetically repelled from it: The protein remains constrained within the small space mentioned above without contacting the inner surface for correct folding. The structural and inner-surface properties of the chaperonin or Complex are controlled by the adenosine triphosphate (ATP) binding to the chaperonin, hydrolysis of ATP into adenosine diphosphate (ADP) and Pi, and dissociation of ADP and Pi. The function of the chaperonin system is exhibited by synchronizing the chemical cycle of ATP hydrolysis with hydration properties of a protein in the water confined on the scale of a nanometer which are substantially different from those in the bulk water.
Dulin D. - One of the best experts on this subject based on the ideXlab platform.
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Temperature controlled high-throughput magnetic tweezers show striking difference in activation energies of replicating viral RNA-dependent RNA polymerases
'Oxford University Press (OUP)', 2020Co-Authors: Seifert M., Van Nies P., Papini F., Arnold J., Poranen M., Cameron C., Depken M., Dulin D.Abstract:RNA virus survival depends on efficient viral genome replication, which is performed by the viral RNA dependent RNA polymerase (RdRp). The recent development of high throughput magnetic tweezers has enabled the simultaneous observation of dozens of viral RdRp elongation traces on kilobases long templates, and this has shown that RdRp nucleotide addition kinetics is stochastically interrupted by rare pauses of 1–1000 s duration, of which the short-lived ones (1–10 s) are the temporal signature of a low fidelity catalytic pathway. We present a simple and precise temperature controlled system for magnetic tweezers to characterize the replication kinetics temperature dependence between 25°C and 45°C of RdRps from three RNA viruses, i.e. the double-stranded RNA bacteriophage Φ6, and the positive-sense single-stranded RNA poliovirus (PV) and human rhinovirus C (HRV-C). We found that Φ6 RdRp is largely temperature insensitive, while PV and HRV-C RdRps replication kinetics are activated by temperature. Furthermore, the activation energies we measured for PV RdRp catalytic state corroborate previous estimations from ensemble pre-steady state kinetic studies, further confirming the catalytic origin of the short pauses and their link to temperature independent RdRp fidelity. This work will enable future temperature controlled study of Biomolecular Complex at the single molecule level
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Temperature controlled high-throughput magnetic tweezers show striking difference in activation energies of replicating viral RNA-dependent RNA polymerases
'Oxford University Press (OUP)', 2020Co-Authors: Seifert Mona, Depken M., Van Nies Pauline, Papini, Flávia S., Arnold, Jamie J., Poranen, Minna M., Cameron, Craig E., Dulin D.Abstract:RNA virus survival depends on efficient viral genome replication, which is performed by the viral RNA dependent RNA polymerase (RdRp). The recent development of high throughput magnetic tweezers has enabled the simultaneous observation of dozens of viral RdRp elongation traces on kilobases long templates, and this has shown that RdRp nucleotide addition kinetics is stochastically interrupted by rare pauses of 1-1000 s duration, of which the short-lived ones (1-10 s) are the temporal signature of a low fidelity catalytic pathway. We present a simple and precise temperature controlled system for magnetic tweezers to characterize the replication kinetics temperature dependence between 25°C and 45°C of RdRps from three RNA viruses, i.e. the double-stranded RNA bacteriophage Φ6, and the positive-sense single-stranded RNA poliovirus (PV) and human rhinovirus C (HRV-C). We found that Φ6 RdRp is largely temperature insensitive, while PV and HRV-C RdRps replication kinetics are activated by temperature. Furthermore, the activation energies we measured for PV RdRp catalytic state corroborate previous estimations from ensemble pre-steady state kinetic studies, further confirming the catalytic origin of the short pauses and their link to temperature independent RdRp fidelity. This work will enable future temperature controlled study of Biomolecular Complex at the single molecule level.BN/Martin Depken LabBN/Nynke Dekker La
Hirokazu Mishima - One of the best experts on this subject based on the ideXlab platform.
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physics of multidrug efflux through a Biomolecular Complex
Biophysical Journal, 2014Co-Authors: Hirokazu Mishima, Hiraku Oshima, Satoshi Yasuda, Kenichi Amano, Masahiro KinoshitaAbstract:Insertion and release of a solute into and from a vessel comprising biopolymers is a fundamental function. A typical example is found in a multidrug efflux transporter. “Multidrug efflux” signifies that solutes such as drug molecules with diverse properties can be handled. In earlier works, we showed that the spatial distribution of the solute-vessel potential of mean force (PMF) induced by the solvent plays imperative roles in the insertion/release process. The PMF can be decomposed into the energetic and entropic components. The entropic component, which originates from the translational displacement of solvent molecules, is rather insensitive to the solute-solvent and vessel inner surface-solvent affinities. This feature is not shared with the energetic component. When the vessel inner surface is neither solvophobic nor solvophilic, the solvents within the vessel cavity and in the bulk offer almost the same environment to any solute, and the energetic component becomes much smaller than the entropic component. Our idea is that the multidrug efflux can be realized if the insertion/release process is accomplished by the entropic component. However, we have recently argued that the entropic release is not feasible as long as the vessel geometry is fixed. Here we consider a model of TolC, a cylindrical vessel possessing an entrance at one end and an exit at the other end for the solute. The spatial distribution of the PMF is calculated by employing the three-dimensional integral equation theory with rigid-body models whose behavior is purely entropic in origin. We show that the entropically inserted solute can be released by a continuous variation of the vessel geometry which forms a time-dependent entropic force continuing to accelerate the solute motion to the exit. Solutes with a wide range of sizes are entropically released using the same vessel-geometry variation.
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on the physics of multidrug efflux through a Biomolecular Complex
Journal of Chemical Physics, 2013Co-Authors: Hirokazu Mishima, Hiraku Oshima, Satoshi Yasuda, Kenichi Amano, Masahiro KinoshitaAbstract:Insertion and release of a solute into and from a vessel comprising biopolymers is a fundamental function in a biological system. A typical example is found in a multidrug efflux transporter. “Multidrug efflux” signifies that solutes such as drug molecules with diverse properties can be handled. In our view, the mechanism of the multidrug efflux is not chemically specific but rather has to be based on a physical factor. In earlier works, we showed that the spatial distribution of the solute-vessel potential of mean force (PMF) induced by the solvent plays imperative roles in the insertion/release process. The PMF can be decomposed into the energetic and entropic components. The entropic component, which originates from the translational displacement of solvent molecules, is rather insensitive to the solute-solvent and vessel inner surface-solvent affinities. This feature is not shared with the energetic component. When the vessel inner surface is neither solvophobic nor solvophilic, the solvents within the vessel cavity and in the bulk offer almost the same environment to any solute with solvophobicity or solvophilicity, and the energetic component becomes much smaller than the entropic component (i.e., the latter predominates over the former). Our idea is that the multidrug efflux can be realized if the insertion/release process is accomplished by the entropic component exhibiting the insensitivity to the solute properties. However, we have recently argued that the entropic release of the solute is not feasible as long as the vessel geometry is fixed. Here we consider a model of TolC, a cylindrical vessel possessing an entrance at one end and an exit at the other end for the solute. The spatial distribution of the PMF is calculated by employing the three-dimensional integral equation theory with rigid-body models in which the constituents interact only through hard-body potentials. Since the behavior of these models is purely entropic in origin, our analysis is focused on the entropic component. We show that the entropically inserted solute can be released by a continuous variation of the vessel geometry which forms a time-dependent entropic force continuing to accelerate the solute motion to the exit. Solutes with a wide range of sizes are entropically released using the same vessel-geometry variation. The results obtained are fairly general and also applicable to the efflux pump protein AcrB and ATP-binding cassette transporter.