The Experts below are selected from a list of 160770 Experts worldwide ranked by ideXlab platform
Ignacio Tinoco - One of the best experts on this subject based on the ideXlab platform.
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An mRNA Downstream Structure Promotes Frameshifting by Destabilizing the Hybrid State and Impeding the EF-G Driven Translocation Process
Biophysical Journal, 2014Co-Authors: Ruben L Gonzalez, Carlos Bustamante, Ignacio TinocoAbstract:Translational frameshifting occurs when a ribosome slips one or two nucleotides on a messenger RNA and generates a new sequence of amino acids. Many viral RNAs have programed frameshift-promoting signals to produce their proteins in the precise ratio needed for their viability. We used single-molecule fluorescence resonance energy transfer (smFRET) to study the dynamics of −1 programmed frameshifting by the dnaX gene in E. coli. The frameshifting mRNA has the usual three prokaryotic frameshifting signals: an internal Shine-Dalgarno sequence, a slippery sequence, and a stem loop. One round of translational elongation of the slippery sequence was characterized by the FRET changes between a Cy3-labeled L1 stalk in the 50S subunit and a Cy5-tRNALys in the P-site. We observed that the downstream stem loop, a critical signal for efficient frameshifting, destabilizes the Hybrid State and thus shifts the equilibrium toward to the classical State of pre-translocation complexes. Translocation catalyzed by EF-G was significantly slower in the frameshifting mRNA than in the non-frameshifting mRNA lacking the stem loop. Furthermore, pre-translocation complexes of the frameshifting mRNA underwent several transitions between the classical and Hybrid States in the presence of EF-G prior to complete translocation, while the majority of the non-frameshifting mRNA translocated rapidly via a single Hybrid State. Quantitative analysis showed that the stem loop impedes EF-G driven translocation in the 30S subunit by elevating the activation barriers to translocation, and leaves the EF-G bound-Hybrid State in dynamic equilibrium with the Hybrid and classical States. We propose that by keeping the ribosome and tRNAs in the dynamically transiting pre-translocation States, the frameshifting mRNA allows more time for the ribosome to explore other paths, such as −1 frameshifting.
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An mRNA Downstream Structure Promotes Frameshifting by Destabilizing the Hybrid State and Impeding the EF-G Driven Translocation Process
Biophysical Journal, 2014Co-Authors: Ruben L Gonzalez, Carlos Bustamante, Ignacio TinocoAbstract:Translational frameshifting occurs when a ribosome slips one or two nucleotides on a messenger RNA and generates a new sequence of amino acids. Many viral RNAs have programed frameshift-promoting signals to produce their proteins in the precise ratio needed for their viability. We used single-molecule fluorescence resonance energy transfer (smFRET) to study the dynamics of −1 programmed frameshifting by the dnaX gene in E. coli. The frameshifting mRNA has the usual three prokaryotic frameshifting signals: an internal Shine-Dalgarno sequence, a slippery sequence, and a stem loop. One round of translational elongation of the slippery sequence was characterized by the FRET changes between a Cy3-labeled L1 stalk in the 50S subunit and a Cy5-tRNALys in the P-site. We observed that the downstream stem loop, a critical signal for efficient frameshifting, destabilizes the Hybrid State and thus shifts the equilibrium toward to the classical State of pre-translocation complexes. Translocation catalyzed by EF-G was significantly slower in the frameshifting mRNA than in the non-frameshifting mRNA lacking the stem loop. Furthermore, pre-translocation complexes of the frameshifting mRNA underwent several transitions between the classical and Hybrid States in the presence of EF-G prior to complete translocation, while the majority of the non-frameshifting mRNA translocated rapidly via a single Hybrid State. Quantitative analysis showed that the stem loop impedes EF-G driven translocation in the 30S subunit by elevating the activation barriers to translocation, and leaves the EF-G bound-Hybrid State in dynamic equilibrium with the Hybrid and classical States. We propose that by keeping the ribosome and tRNAs in the dynamically transiting pre-translocation States, the frameshifting mRNA allows more time for the ribosome to explore other paths, such as −1 frameshifting.
Arda Kurt - One of the best experts on this subject based on the ideXlab platform.
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Discrete-State Encoding in Hybrid-State Systems for Intelligent Vehicle Control and Estimation
IEEE Transactions on Intelligent Transportation Systems, 2015Co-Authors: Arda KurtAbstract:This paper develops an encoding scheme for discrete-State systems as part of a Hybrid-State hierarchy. The codes are based on commands between subsystems, in the sense that the interactions of the discrete States with the continuous States are exploited to attach significance to what each discrete State does to the continuous subsystem. The resultant codeset is independent of how the discrete-State transitions are designed, and conventional tools such as truth tables and K-maps are easily applicable in the binary representation of the codes. Code-based representations of every possible combination of commands/behaviors governed by the discrete subsystem is useful in a number of design scenarios, an example of which is the generation of a consistent norm for discrete States. Such a norm is demonstrated to be useful in Hybrid-State estimation.
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ICCPS - Poster Abstract: Hierarchical Hybrid-State Systems for Coordinated Autonomous Driving in Mixed-Traffic Urban Environments
2012 IEEE ACM Third International Conference on Cyber-Physical Systems, 2012Co-Authors: Arda Kurt, Scott Biddlestone, Keith Redmill, Umit OzgunerAbstract:This study focuses on a number of control and coordination aspects of autonomous navigation in real-life urban traffic. By expanding the inherent hierarchy of the Hybrid-State system formulation, a highly-structured yet modular architecture was developed to connect various traffic elements. The feasibility of coordination under vehicle-to-vehicle and vehicle-to-infrastructure communication was investigated through experiments with multiple vehicles and roadside units. The necessary levels of situational awareness abstractions for different tiers of the proposed hierarchy were studied on stochastic Hybrid-State system estimators.
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ITSC - Hybrid-State driver/vehicle modelling, estimation and prediction
13th International IEEE Conference on Intelligent Transportation Systems, 2010Co-Authors: Arda Kurt, John L. Yester, Yutaka Mochizuki, Umit OzgunerAbstract:The first part of this study develops a general architecture for estimation and prediction of Hybrid-State systems. The proposed system utilizes the Hybrid characteristics of decision-behaviour coupling of many systems such as the driver and the vehicle; uses estimates of observable parameters to track instantaneous discrete State and predicts the most likely outcome, depending on the discrete model and the observed behaviour of the continuous subsystem. The proposed method is suitable for the scenarios that involve unknown decisions of other individuals, such as lane changes or intersection precedence/access. In the second part, this paper specifically deals with the implementation of the proposed methodology on an intersection safety system, predicting the vehicle behaviours and potential outcomes through traffic intersection scenarios. Driver intentions are tracked and predicted through vehicle behaviour, and possible combinations of intention predictions for different vehicles are interpreted for the safety of the situation.
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Hybrid State System Development for Autonomous Vehicle Control in Urban Scenarios
IFAC Proceedings Volumes, 2008Co-Authors: Arda Kurt, Umit OzgunerAbstract:Abstract This paper analyzes a Hybrid-State-system-based controller for an autonomous vehicle in urban traffic and provides development procedures for Hybrid-State systems for automatic control. The Ohio-State University Autonomous City Transport utilizes a discrete-State system, based on a finite State machine for high-level decision making and a continuous-State controller for low-level lateral and longitudinal control. The design procedure for the overall Hybrid controller involves a series of capability grafts, each improving the ability of the vehicle to handle diverse situations. The design methodology, as demonstrated in a number of development steps, and architecture are capable of handling various urban scenarios, as demonstrated in a June 2007 site visit by Darpa officials.
Paul C. Whitford - One of the best experts on this subject based on the ideXlab platform.
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A steric gate controls P/E Hybrid-State formation of tRNA on the ribosome.
Nature communications, 2020Co-Authors: Mariana Levi, Kelsey N. Walak, Ailun Wang, Udayan Mohanty, Paul C. WhitfordAbstract:The ribosome is a biomolecular machine that undergoes multiple large-scale structural rearrangements during protein elongation. Here, we focus on a conformational rearrangement during translocation, known as P/E Hybrid-State formation. Using a model that explicitly represents all non-hydrogen atoms, we simulated more than 120 spontaneous transitions, where the tRNA molecule is displaced between the P and E sites of the large subunit. In addition to predicting a free-energy landscape that is consistent with previous experimental observations, the simulations reveal how a six-residue gate-like region can limit P/E formation, where sub-angstrom structural perturbations lead to an order-of-magnitude change in kinetics. Thus, this precisely defined set of residues represents a novel target that may be used to control functional dynamics in bacterial ribosomes. This theoretical analysis establishes a direct relationship between ribosome structure and large-scale dynamics, and it suggests how next-generation experiments may precisely dissect the energetics of Hybrid formation on the ribosome. The ribosome undergoes multiple large-scale structural rearrangements during protein elongation. Here the authors present an all-atom model of the ribosome to study the energetics of P/E Hybrid-State formation, an early conformational rearrangement occurring during translocation.
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Capturing Transition States for tRNA Hybrid-State Formation in the Ribosome
The journal of physical chemistry. B, 2016Co-Authors: Kien Nguyen, Paul C. WhitfordAbstract:In order to quantitatively describe the energetics of biomolecular rearrangements, it is necessary to identify reaction coordinates that accurately capture the relevant transition events. Here, we perform simulations of A-site tRNA movement (∼20 A) during Hybrid-State formation in the ribosome and quantify the ability of interatomic distances to capture the transition State ensemble. Numerous coordinates are found to be accurate indicators of the transition State, allowing tRNA rearrangements to be described as diffusion across a one-dimensional free-energy surface. In addition to providing insights into the physical-chemical relationship between biomolecular structure and dynamics, these results can help enable single-molecule techniques to probe the free-energy landscape of the ribosome.
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Simulating movement of tRNA through the ribosome during Hybrid-State formation.
The Journal of chemical physics, 2013Co-Authors: Paul C. Whitford, Karissa Y. SanbonmatsuAbstract:Biomolecular simulations provide a means for exploring the relationship between flexibility, energetics, structure, and function. With the availability of atomic models from X-ray crystallography and cryoelectron microscopy (cryo-EM), and rapid increases in computing capacity, it is now possible to apply molecular dynamics (MD) simulations to large biomolecular machines, and systematically partition the factors that contribute to function. A large biomolecular complex for which atomic models are available is the ribosome. In the cell, the ribosome reads messenger RNA (mRNA) in order to synthesize proteins. During this essential process, the ribosome undergoes a wide range of conformational rearrangements. One of the most poorly understood transitions is translocation: the process by which transfer RNA (tRNA) molecules move between binding sites inside of the ribosome. The first step of translocation is the adoption of a “Hybrid” configuration by the tRNAs, which is accompanied by large-scale rotations in the ribosomal subunits. To illuminate the relationship between these rearrangements, we apply MD simulations using a multi-basin structure-based (SMOG) model, together with targeted molecular dynamics protocols. From 120 simulated transitions, we demonstrate the viability of a particular route during P/E Hybrid-State formation, where there is asynchronous movement along rotation and tRNA coordinates. These simulations not only suggest an ordering of events, but they highlight atomic interactions that may influence the kinetics of Hybrid-State formation. From these simulations, we also identify steric features (H74 and surrounding residues) encountered during the Hybrid transition, and observe that flexibility of the single-stranded 3′-CCA tail is essential for it to reach the endpoint. Together, these simulations provide a set of structural and energetic signatures that suggest strategies for modulating the physical-chemical properties of protein synthesis by the ribosome.
Ruben L Gonzalez - One of the best experts on this subject based on the ideXlab platform.
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An mRNA Downstream Structure Promotes Frameshifting by Destabilizing the Hybrid State and Impeding the EF-G Driven Translocation Process
Biophysical Journal, 2014Co-Authors: Ruben L Gonzalez, Carlos Bustamante, Ignacio TinocoAbstract:Translational frameshifting occurs when a ribosome slips one or two nucleotides on a messenger RNA and generates a new sequence of amino acids. Many viral RNAs have programed frameshift-promoting signals to produce their proteins in the precise ratio needed for their viability. We used single-molecule fluorescence resonance energy transfer (smFRET) to study the dynamics of −1 programmed frameshifting by the dnaX gene in E. coli. The frameshifting mRNA has the usual three prokaryotic frameshifting signals: an internal Shine-Dalgarno sequence, a slippery sequence, and a stem loop. One round of translational elongation of the slippery sequence was characterized by the FRET changes between a Cy3-labeled L1 stalk in the 50S subunit and a Cy5-tRNALys in the P-site. We observed that the downstream stem loop, a critical signal for efficient frameshifting, destabilizes the Hybrid State and thus shifts the equilibrium toward to the classical State of pre-translocation complexes. Translocation catalyzed by EF-G was significantly slower in the frameshifting mRNA than in the non-frameshifting mRNA lacking the stem loop. Furthermore, pre-translocation complexes of the frameshifting mRNA underwent several transitions between the classical and Hybrid States in the presence of EF-G prior to complete translocation, while the majority of the non-frameshifting mRNA translocated rapidly via a single Hybrid State. Quantitative analysis showed that the stem loop impedes EF-G driven translocation in the 30S subunit by elevating the activation barriers to translocation, and leaves the EF-G bound-Hybrid State in dynamic equilibrium with the Hybrid and classical States. We propose that by keeping the ribosome and tRNAs in the dynamically transiting pre-translocation States, the frameshifting mRNA allows more time for the ribosome to explore other paths, such as −1 frameshifting.
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An mRNA Downstream Structure Promotes Frameshifting by Destabilizing the Hybrid State and Impeding the EF-G Driven Translocation Process
Biophysical Journal, 2014Co-Authors: Ruben L Gonzalez, Carlos Bustamante, Ignacio TinocoAbstract:Translational frameshifting occurs when a ribosome slips one or two nucleotides on a messenger RNA and generates a new sequence of amino acids. Many viral RNAs have programed frameshift-promoting signals to produce their proteins in the precise ratio needed for their viability. We used single-molecule fluorescence resonance energy transfer (smFRET) to study the dynamics of −1 programmed frameshifting by the dnaX gene in E. coli. The frameshifting mRNA has the usual three prokaryotic frameshifting signals: an internal Shine-Dalgarno sequence, a slippery sequence, and a stem loop. One round of translational elongation of the slippery sequence was characterized by the FRET changes between a Cy3-labeled L1 stalk in the 50S subunit and a Cy5-tRNALys in the P-site. We observed that the downstream stem loop, a critical signal for efficient frameshifting, destabilizes the Hybrid State and thus shifts the equilibrium toward to the classical State of pre-translocation complexes. Translocation catalyzed by EF-G was significantly slower in the frameshifting mRNA than in the non-frameshifting mRNA lacking the stem loop. Furthermore, pre-translocation complexes of the frameshifting mRNA underwent several transitions between the classical and Hybrid States in the presence of EF-G prior to complete translocation, while the majority of the non-frameshifting mRNA translocated rapidly via a single Hybrid State. Quantitative analysis showed that the stem loop impedes EF-G driven translocation in the 30S subunit by elevating the activation barriers to translocation, and leaves the EF-G bound-Hybrid State in dynamic equilibrium with the Hybrid and classical States. We propose that by keeping the ribosome and tRNAs in the dynamically transiting pre-translocation States, the frameshifting mRNA allows more time for the ribosome to explore other paths, such as −1 frameshifting.
Zhao Jun - One of the best experts on this subject based on the ideXlab platform.
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A Method of Hybrid State-feedback guaranteed cost control and optimization design for uncertain linear time-delay system
Control theory & applications, 2006Co-Authors: Zhao JunAbstract:This paper focuses on the Hybrid Statefeedback guaranteed cost control and optimization design problem for a class of uncertain linear time-delay systems.Suppose that there exist finite candidate controllers with known controller gain matrices and none of the controllers can make the system satisfy guaranteed cost control,based on single-Lyapunov function method we obtained the sufficient conditions and optimization scheme for the Hybrid State-feedback guaranteed cost control.When the controller gain matrices are unknown,by means of multiple function technique,a sufficient condition and optimization scheme are also presented for Hybrid State-feedback guaranteed cost control.The simulation demonstrates the effectiveness of the method proposed in this paper.
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Hybrid State-Feedback Reliable H_∞ Control for a Class of Uncertain Linear Systems
Systems Engineering - Theory & Practice, 2006Co-Authors: Zhao JunAbstract:This paper studies the Hybrid State-feedback reliable H_∞ problem for a class of uncertain linear systems.Suppose there exist finite candidate controllers and actuators suffer "serious failure"—the never failed actuators can not stabilize the given system,then none of the controllers can make the system stable and satisfy H_∞ control.Based on multiple Lyapunov function technique,a sufficient condition for the existence of the Hybrid State feedback reliable H_∞ controller is obtained by means of switching among candidate controllers.The corresponding results are given in terms of linear matrix inequalities (LMI).Finally,a numerical example illustrates the effectiveness of the proposed approaches.
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Hybrid State-feedback guaranteed cost control for a class of uncertain linear systems
Control and Decision, 2005Co-Authors: Zhao JunAbstract:The Hybrid State-feedback guaranteed control problem for a class of uncertain linear systems is discussed. Time-varying uncertainties are contained in both State matrix and input matrix. Based on single Lyapunov function method, sufficient conditions for Hybrid State-feedback guaranteed cost control are given and the switching laws are constructed . When the controller gain matrices are unknown, a sufficient condition for Hybrid State-feedback guaranteed cost control is also derived by means of multiple function technique. The simulation result shows the effectiveness of the proposed method.
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H_∞ Robust Control of a Class of Linear Systems Via Hybrid State Feedback
Journal of Northeastern University, 2003Co-Authors: Zhao JunAbstract:The H ∞ robust stabilization for a class of linear systems was studied via Hybrid State feedback strategy. Suppose that there exist finite candidate static-State feedback controllers with known gain matrix,and the systems are unstable using a single controller, in terms of the condition of convex combination and the design of switching laws, a sufficient condition for H ∞ robust stabilization of the system was derived through switching among the controllers. The sufficient condition can be given by linear matrix inequalities.
