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Shi-jie Chen - One of the best experts on this subject based on the ideXlab platform.
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Predicting Cotranscriptional Folding Kinetics For Riboswitch.
Journal of Physical Chemistry B, 2018Co-Authors: Chenhan Zhao, Shi-jie ChenAbstract:On the basis of a helix-based transition rate model, we developed a new method for sampling cotranscriptional RNA conformational ensemble and the prediction of cotranscriptional Folding Kinetics. Applications to E. coli. SRP RNA and pbuE riboswitch indicate that the model may provide reliable predictions for the cotranscriptional Folding pathways and population Kinetics. For E. coli. SRP RNA, the predicted population Kinetics and the Folding pathway are consistent with the SHAPE profiles in the recent cotranscriptional SHAPE-seq experiments. For the pbuE riboswitch, the model predicts the transcriptional termination efficiency as a function of the force. The theoretical results show (a) a force-induced transition from the aptamer (antiterminator) to the terminator structure and (b) the different Folding pathways for the riboswitch with and without the ligand (adenine). More specifically, without adenine, the aptamer structure emerges as a short-lived kinetic transient state instead of a thermodynamically ...
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Predicting Cotranscriptional Folding Kinetics For Riboswitch.
The journal of physical chemistry. B, 2018Co-Authors: Ting-ting Sun, Chenhan Zhao, Shi-jie ChenAbstract:On the basis of a helix-based transition rate model, we developed a new method for sampling cotranscriptional RNA conformational ensemble and the prediction of cotranscriptional Folding Kinetics. Applications to E. coli. SRP RNA and pbuE riboswitch indicate that the model may provide reliable predictions for the cotranscriptional Folding pathways and population Kinetics. For E. coli. SRP RNA, the predicted population Kinetics and the Folding pathway are consistent with the SHAPE profiles in the recent cotranscriptional SHAPE-seq experiments. For the pbuE riboswitch, the model predicts the transcriptional termination efficiency as a function of the force. The theoretical results show (a) a force-induced transition from the aptamer (antiterminator) to the terminator structure and (b) the different Folding pathways for the riboswitch with and without the ligand (adenine). More specifically, without adenine, the aptamer structure emerges as a short-lived kinetic transient state instead of a thermodynamically stable intermediate state. Furthermore, from the predicted extension-time curves, the model identifies a series of conformational switches in the pulling process, where the predicted relative residence times for the different structures are in accordance with the experimental data. The model may provide a new tool for quantitative predictions of cotranscriptional Folding Kinetics, and results can offer useful insights into cotranscriptional Folding-related RNA functions such as regulation of gene expression with riboswitches.
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Cotranscriptional Folding Kinetics of ribonucleic acid secondary structures.
The Journal of chemical physics, 2011Co-Authors: Peinan Zhao, Wenbing Zhang, Shi-jie ChenAbstract:We develop a systematic helix-based computational method to predict RNA Folding Kinetics during transcription. In our method, the transcription is modeled as stepwise process, where each step is the transcription of a nucleotide. For each step, the Kinetics algorithm predicts the population Kinetics, transition pathways, Folding intermediates, and the transcriptional Folding products. The Folding pathways, rate constants, and the conformational populations for cotranscription Folding show contrastingly different features than the reFolding Kinetics for a fully transcribed chain. The competition between the transcription speed and rate constants for the transitions between the different nascent structures determines the RNA Folding pathway and the end product of Folding. For example, fast transcription favors the formation of branch-like structures than rod-like structures and chain elongation in the Folding process may reduce the probability of the formation of misfolded structures. Furthermore, good theory-experiment agreements suggest that our method may provide a reliable tool for quantitative prediction for cotranscriptional RNA Folding, including the Kinetics for the population distribution for the whole conformational ensemble.
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Folding Kinetics for the Conformational Switch Between Alternative RNA Structures
Biophysical Journal, 2011Co-Authors: Song Cao, Boris Fürtig, Harald Schwalbe, Shi-jie ChenAbstract:The conformational switching between different conformational states is intrinsic to RNA catalytic and regulatory functions, which oftenly occurs on time-scales of several seconds. In combination with the recent real-time NMR experiments (Wenter et al. Angew. Chem. Int. Ed. (2005). 44, 2600; Wenter et al. ChemBioChem. (2006). 7, 417) for the transitions between bistable RNA conformations, we combine the master equation method with the kinetic cluster method to investigate the detailed kinetic mechanism and the factors that govern the Folding Kinetics. Based on the computational studies, we propose that heat capacity change upon RNA Folding may be important for RNA Folding Kinetics. In addition, we find that noncanonical (tertiary) intraloop interactions in tetraloop hairpins are important to determine the Folding Kinetics. Furthermore, through theory-experiment comparisons, we find that the different rate models for the fundamental steps (i.e., formation/disruption of a base pair or stack) can cause contrasting results in the theoretical predictions.
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Folding Kinetics for the Conformational Switch between Alternative RNA Structures
The journal of physical chemistry. B, 2010Co-Authors: Song Cao, Boris Fürtig, Harald Schwalbe, Shi-jie ChenAbstract:Transitions between different conformational states, so-called conformational switching, are intrinsic to RNA catalytic and regulatory functions. Often, conformational switching occurs on time scales of several seconds. In combination with the recent real-time NMR experiments (Wenter et al. Angew. Chem. Int. Ed. 2005, 44, 2600; Wenter et al. ChemBioChem 2006, 7, 417) for the transitions between bistable RNA conformations, we combine the master equation method with the kinetic cluster method to investigate the detailed kinetic mechanism and the factors that govern the Folding Kinetics. We propose that heat capacity change (ΔCp) upon RNA Folding may be important for RNA Folding Kinetics. In addition, we find that, for tetraloop hairpins, noncanonical (tertiary) intraloop interactions are important to determine the Folding Kinetics. Furthermore, through theory−experiment comparisons, we find that the different rate models for the fundamental steps (i.e., formation/disruption of a base pair or stack) can caus...
Nancy M. Amato - One of the best experts on this subject based on the ideXlab platform.
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Simulating RNA Folding Kinetics on approximated energy landscapes.
Journal of molecular biology, 2008Co-Authors: Xinyu Tang, Thomas Shawna L, Lydia Tapia, David P. Giedroc, Nancy M. AmatoAbstract:We present a general computational approach to simulate RNA Folding Kinetics that can be used to extract population Kinetics, Folding rates and the formation of particular substructures that might be intermediates in the Folding process. Simulating RNA Folding Kinetics can provide unique insight into RNA whose functions are dictated by Folding Kinetics and not always by nucleotide sequence or the structure of the lowest free-energy state. The method first builds an approximate map (or model) of the Folding energy landscape from which the population Kinetics are analyzed by solving the master equation on the map. We present results obtained using an analysis technique, map-based Monte Carlo simulation, which stochastically extracts Folding pathways from the map. Our method compares favorably with other computational methods that begin with a comprehensive free-energy landscape, illustrating that the smaller, approximate map captures the major features of the complete energy landscape. As a result, our method scales to larger RNAs. For example, here we validate Kinetics of RNA of more than 200 nucleotides. Our method accurately computes the Kinetics-based functional rates of wild-type and mutant ColE1 RNAII and MS2 phage RNAs showing excellent agreement with experiment.
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Using motion planning to study RNA Folding Kinetics.
Journal of computational biology : a journal of computational molecular cell biology, 2005Co-Authors: Xinyu Tang, Shawna Thomas, Bonnie Kirkpatrick, Guang Song, Nancy M. AmatoAbstract:We propose a novel, motion planning based approach to approximately map the energy landscape of an RNA molecule. A key feature of our method is that it provides a sparse map that captures the main features of the energy landscape which can be analyzed to compute Folding Kinetics. Our method is based on probabilistic roadmap motion planners that we have previously successfully applied to protein Folding. In this paper, we provide evidence that this approach is also well suited to RNA. We compute population Kinetics and transition rates on our roadmaps using the master equation for a few moderately sized RNA and show that our results compare favorably with results of other existing methods.
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RECOMB - Using motion planning to study RNA Folding Kinetics
Proceedings of the eighth annual international conference on Computational molecular biology - RECOMB '04, 2004Co-Authors: Xinyu Tang, Shawna Thomas, Bonnie Kirkpatrick, Guang Song, Nancy M. AmatoAbstract:We propose a novel, motion planning based approach to approximately map the energy landscape of an RNA molecule. Our method is based on the successful probabilistic roadmap motion planners that we have previously successfully applied to protein Folding. The key advantage of our method is that it provides a sparse map that captures the main features of the landscape and which can be analyzed to compute Folding Kinetics. In this paper, we provide evidence that this approach is also well suited to RNA. We compute population Kinetics and transition rates on our roadmaps using the master equation for a few moderately sized RNA and show that our results compare favorably with results of other existing methods.
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Using motion planning to map protein Folding landscapes and analyze Folding Kinetics of known native structures.
Journal of computational biology : a journal of computational molecular cell biology, 2003Co-Authors: Nancy M. Amato, Ken A. Dill, Guang SongAbstract:We investigate a novel approach for studying the Kinetics of protein Folding. Our framework has evolved from robotics motion planning techniques called probabilistic roadmap methods (PRMs) that have been applied in many diverse fields with great success. In our previous work, we presented our PRM-based technique and obtained encouraging results studying protein Folding pathways for several small proteins. In this paper, we describe how our motion planning framework can be used to study protein Folding Kinetics. In particular, we present a refined version of our PRM-based framework and describe how it can be used to produce potential energy landscapes, free energy landscapes, and many Folding pathways all from a single roadmap which is computed in a few hours on a desktop PC. Results are presented for 14 proteins. Our ability to produce large sets of unrelated Folding pathways may potentially provide crucial insight into some aspects of Folding Kinetics, such as proteins that exhibit both two-state and three-state Kinetics that are not captured by other theoretical techniques.
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using motion planning to map protein Folding landscapes and analyze Folding Kinetics of known native structures
Research in Computational Molecular Biology, 2002Co-Authors: Nancy M. Amato, Ken A. Dill, Guang SongAbstract:We present a novel approach for studying the Kinetics of protein Folding. The framework has evolved from robotics motion planning techniques called probabilistic roadmap methods (prms) that have been applied in many diverse fields with great success. In our previous work, we used a Prm-based technique to study protein Folding pathways of several small proteins and obtained encouraging results. In this paper, we describe how our motion planning framework can be used to study protein Folding Kinetics. In particular, we present a refined version of our Prm-based framework and describe how it can be used to produce potential energy landscapes, free energy landscapes, and many Folding pathways all from a single roadmap which is computed in a few hours on a desktop PC. Results are presented for 14 proteins. Our ability to produce large sets of unrelated Folding pathways may potentially provide crucial insight into some aspects of Folding Kinetics, such as proteins that exhibit both two-state and three-state Kinetics, that are not captured by other theoretical techniques.
Chenhan Zhao - One of the best experts on this subject based on the ideXlab platform.
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Predicting Cotranscriptional Folding Kinetics For Riboswitch.
Journal of Physical Chemistry B, 2018Co-Authors: Chenhan Zhao, Shi-jie ChenAbstract:On the basis of a helix-based transition rate model, we developed a new method for sampling cotranscriptional RNA conformational ensemble and the prediction of cotranscriptional Folding Kinetics. Applications to E. coli. SRP RNA and pbuE riboswitch indicate that the model may provide reliable predictions for the cotranscriptional Folding pathways and population Kinetics. For E. coli. SRP RNA, the predicted population Kinetics and the Folding pathway are consistent with the SHAPE profiles in the recent cotranscriptional SHAPE-seq experiments. For the pbuE riboswitch, the model predicts the transcriptional termination efficiency as a function of the force. The theoretical results show (a) a force-induced transition from the aptamer (antiterminator) to the terminator structure and (b) the different Folding pathways for the riboswitch with and without the ligand (adenine). More specifically, without adenine, the aptamer structure emerges as a short-lived kinetic transient state instead of a thermodynamically ...
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Predicting Cotranscriptional Folding Kinetics For Riboswitch.
The journal of physical chemistry. B, 2018Co-Authors: Ting-ting Sun, Chenhan Zhao, Shi-jie ChenAbstract:On the basis of a helix-based transition rate model, we developed a new method for sampling cotranscriptional RNA conformational ensemble and the prediction of cotranscriptional Folding Kinetics. Applications to E. coli. SRP RNA and pbuE riboswitch indicate that the model may provide reliable predictions for the cotranscriptional Folding pathways and population Kinetics. For E. coli. SRP RNA, the predicted population Kinetics and the Folding pathway are consistent with the SHAPE profiles in the recent cotranscriptional SHAPE-seq experiments. For the pbuE riboswitch, the model predicts the transcriptional termination efficiency as a function of the force. The theoretical results show (a) a force-induced transition from the aptamer (antiterminator) to the terminator structure and (b) the different Folding pathways for the riboswitch with and without the ligand (adenine). More specifically, without adenine, the aptamer structure emerges as a short-lived kinetic transient state instead of a thermodynamically stable intermediate state. Furthermore, from the predicted extension-time curves, the model identifies a series of conformational switches in the pulling process, where the predicted relative residence times for the different structures are in accordance with the experimental data. The model may provide a new tool for quantitative predictions of cotranscriptional Folding Kinetics, and results can offer useful insights into cotranscriptional Folding-related RNA functions such as regulation of gene expression with riboswitches.
Wenbing Zhang - One of the best experts on this subject based on the ideXlab platform.
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Folding Kinetics of HDV ribozyme with C13A:G82U and A16U:U79A mutations
Wuhan University Journal of Natural Sciences, 2015Co-Authors: Yanjuan Zou, Yujie Wang, Sha Gong, Wenbing ZhangAbstract:Gene mutations influence the Folding Kinetics of hepatitis delta virus (HDV) ribozyme. In this work, we study the effect of the double mutation on the Folding Kinetics of HDV ribozyme. By using the master equation method combined with RNA Folding free energy landscape, we predict the Folding Kinetics of C13A:G82U and A16U:U79A mutated HDV sequences. Their Folding pathways are identified by recursively searching the states with high net flux-in(out) population starting from the native state. The results indicate that the Folding Kinetics of C13A:G82U mutation sequence is bi-phasic, which is similar to the wild type (wtHDV) sequence. While the Folding Kinetics of A16U:U79A mutation sequence is mono-phasic, it quickly folds to the native state in 30 s. Thus, the Folding Kinetics of double mutated HDV ribozyme depends on the mutation sites.
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RNA Folding: Structure Prediction, Folding Kinetics and Ion Electrostatics
Advances in experimental medicine and biology, 2014Co-Authors: Zhi-jie Tan, Wenbing Zhang, Ya-zhou Shi, Feng-hua WangAbstract:Beyond the “traditional” functions such as gene storage, transport and protein synthesis, recent discoveries reveal that RNAs have important “new” biological functions including the RNA silence and gene regulation of riboswitch. Such functions of noncoding RNAs are strongly coupled to the RNA structures and proper structure change, which naturally leads to the RNA Folding problem including structure prediction and Folding Kinetics. Due to the polyanionic nature of RNAs, RNA Folding structure, stability and Kinetics are strongly coupled to the ion condition of solution. The main focus of this chapter is to review the recent progress in the three major aspects in RNA Folding problem: structure prediction, Folding Kinetics and ion electrostatics. This chapter will introduce both the recent experimental and theoretical progress, while emphasize the theoretical modelling on the three aspects in RNA Folding.
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Cotranscriptional Folding Kinetics of ribonucleic acid secondary structures.
The Journal of chemical physics, 2011Co-Authors: Peinan Zhao, Wenbing Zhang, Shi-jie ChenAbstract:We develop a systematic helix-based computational method to predict RNA Folding Kinetics during transcription. In our method, the transcription is modeled as stepwise process, where each step is the transcription of a nucleotide. For each step, the Kinetics algorithm predicts the population Kinetics, transition pathways, Folding intermediates, and the transcriptional Folding products. The Folding pathways, rate constants, and the conformational populations for cotranscription Folding show contrastingly different features than the reFolding Kinetics for a fully transcribed chain. The competition between the transcription speed and rate constants for the transitions between the different nascent structures determines the RNA Folding pathway and the end product of Folding. For example, fast transcription favors the formation of branch-like structures than rod-like structures and chain elongation in the Folding process may reduce the probability of the formation of misfolded structures. Furthermore, good theory-experiment agreements suggest that our method may provide a reliable tool for quantitative prediction for cotranscriptional RNA Folding, including the Kinetics for the population distribution for the whole conformational ensemble.
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Predicting Secondary Structural Folding Kinetics for Nucleic Acids
Biophysical journal, 2010Co-Authors: Peinan Zhao, Wenbing Zhang, Shi-jie ChenAbstract:We report a new computational approach to the prediction of RNA secondary structure Folding Kinetics. In this approach, each elementary kinetic step is represented as the transformation between two secondary structures that differ by a helix. Based on the free energy landscape analysis, we identify three types of dominant pathways and the rate constants for the kinetic steps: 1), formation; 2), disruption of a helix stem; and 3), helix formation with concomitant partial melting of a competing (incompatible) helix. The third pathway, termed the tunneling pathway, is the low-barrier dominant pathway for the conversion between two incompatible helices. Comparisons with experimental data indicate that this new method is quite reliable in predicting the Kinetics for RNA secondary structural Folding and structural rearrangements. The approach presented here may provide a robust first step for further systematic development of a predictive theory for the Folding Kinetics for large RNAs.
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Exploring the Complex Folding Kinetics of RNA Hairpins: I. General Folding Kinetics Analysis
Biophysical journal, 2005Co-Authors: Wenbing Zhang, Shi-jie ChenAbstract:Depending on the nucleotide sequence, the temperature, and other conditions, RNA hairpin-Folding Kinetics can be very complex. The complexity with a wide range of cooperative and noncooperative kinetic behaviors arises from the interplay between the formation of the loops, the disruption of the misfolded states, and the formation of the rate-limiting base stacks. With a rate constant model and a kinetic-cluster theory, we explore the broad landscape for RNA hairpin-Folding Kinetics. The model is validated through direct tests against several experimental measurements. The general kinetic Folding mechanisms and the predicted great variety of Folding Kinetics are directly applicable and quantitatively testable in experiments. The results from this study suggest that 1), previous experimental findings based on the individual hairpins revealed only a small fraction of much broader and more complex RNA hairpin-Folding landscapes; 2), even for structures as simple as hairpins, universal Folding timescales and pathways do not exist; and 3), to treat the loop size as the sole factor to determine the hairpin-Folding rate is an oversimplification.
Rui Zhou - One of the best experts on this subject based on the ideXlab platform.
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Folding Kinetics of ww domains with the united residue force field for bridging microscopic motions and experimental measurements
Proceedings of the National Academy of Sciences of the United States of America, 2014Co-Authors: Gia G Maisuradze, Rui Zhou, Harold A. Scheraga, Yi Xiao, David Sunol, Toni Todorovski, Maria J Macias, Cezary CzaplewskiAbstract:To demonstrate the utility of the coarse-grained united-residue (UNRES) force field to compare experimental and computed kinetic data for Folding proteins, we have performed long-time millisecond-timescale canonical Langevin molecular dynamics simulations of the triple β-strand from the Formin binding protein 28 WW domain and six nonnatural variants, using UNRES. The results have been compared with available experimental data in both a qualitative and a quantitative manner. Complexities of the Folding pathways, which cannot be determined experimentally, were revealed. The Folding mechanisms obtained from the simulated Folding Kinetics are in agreement with experimental results, with a few discrepancies for which we have accounted. The origins of single- and double-exponential Kinetics and their correlations with two- and three-state Folding scenarios are shown to be related to the relative barrier heights between the various states. The rate constants obtained from time profiles of the fractions of the native, intermediate, and unfolded structures, and the kinetic equations fitted to them, correlate with the experimental values; however, they are about three orders of magnitude larger than the experimental ones for most of the systems. These differences are in agreement with the timescale extension derived by scaling down the friction of water and averaging out the fast degrees of freedom when passing from all-atom to a coarse-grained representation. Our results indicate that the UNRES force field can provide accurate predictions of Folding Kinetics of these WW domains, often used as models for the study of the mechanisms of proein Folding.
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effects of mutation truncation and temperature on the Folding Kinetics of a ww domain
Journal of Molecular Biology, 2012Co-Authors: Gia G Maisuradze, Adam Liwo, Rui Zhou, Yi Xiao, Harold A. ScheragaAbstract:Abstract The purpose of this work is to show how mutation, truncation, and change of temperature can influence the Folding Kinetics of a protein. This is accomplished by principal component analysis of molecular-dynamics-generated Folding trajectories of the triple β-strand WW domain from formin binding protein 28 (FBP28) (Protein Data Bank ID: 1E0L ) and its full-size, and singly- and doubly-truncated mutants at temperatures below and very close to the melting point. The reasons for biphasic Folding Kinetics [i.e., coexistence of slow (three-state) and fast (two-state) phases], including the involvement of a solvent-exposed hydrophobic cluster and another delocalized hydrophobic core in the Folding Kinetics, are discussed. New Folding pathways are identified in free-energy landscapes determined in terms of principal components for full-size mutants. Three-state Folding is found to be a main mechanism for Folding the FBP28 WW domain and most of the full-size and truncated mutants. The results from the theoretical analysis are compared to those from experiment. Agreements and discrepancies between the theoretical and experimental results are discussed. Because of its importance in understanding protein Kinetics and function, the diffusive mechanism by which the FBP28 WW domain and its full-size and truncated mutants explore their conformational space is examined in terms of the mean-square displacement and principal component analysis eigenvalue spectrum analyses. Subdiffusive behavior is observed for all studied systems.