Kinetic Proofreading at Single Molecular Level: Aminoacylation of tRNAIle and the Role of Water as an Editor

Santra, Mantu; Bagchi, Biman

doi:10.1371/journal.pone.0066112

Cited by 4 publications

(5 citation statements)

References 25 publications

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“…In addition, we only addressed four possible criteria, but other characteristic properties may also be optimized to support the functionality of biological systems. It would also be interesting to apply the mathematical formalism and the ranking method to other enzymatic systems that display high fidelity (i.e., low error rates) due to the presence of the KPR mechanism, e.g., aminoacyl-tRNA synthetase. ,, …”

Section: Discussionmentioning

confidence: 99%

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Trade-Offs between Error, Speed, Noise, and Energy Dissipation in Biological Processes with Proofreading

2019

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High accuracy of major biological processes relies on the ability of the participating enzymatic molecules to preferentially select the correct substrate from a pool of chemically similar substrates by activating the so-called proofreading mechanisms. While the importance of such mechanisms is widely accepted, it is still unclear how evolution has optimized the biological systems with respect to certain characteristic properties. Here, using a discrete-state stochastic framework with a first-passage analysis, we theoretically investigate trade-offs between four characteristic properties of enzymatic systems, namely, error, speed, noise, and energy dissipation. Specifically, two fundamental biological processes are examined, i.e., DNA replication in the T7 bacteriophage and tRNA selection during protein translation in Escherichia coli. Notably, all of the characteristic properties cannot be completely optimized at the same time due to trade-offs between them. To understand the relative importance of the computed quantities to the enzymatic functionality, we introduce a new quantitative metric to rank the properties. The results demonstrate that the reaction speed is the principal characteristic property that evolution optimizes in both enzymatic systems and that the energy dissipation comes in second. In addition, the error and the noise are always ranked third and fourth, respectively, regardless of the system considered. Physicochemical arguments to explain these observations are presented.

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Section: Discussionmentioning

confidence: 99%

“…It would also be interesting to apply the mathematical formalism and the ranking method to other enzymatic systems that display high fidelity (i.e., low error rates) due to the presence of the KPR mechanism, e.g., aminoacyl-tRNA synthetase. 22,36,37 ■ ASSOCIATED CONTENT * S Supporting Information…”

Section: ■ Conclusionmentioning

confidence: 99%

Trade-Offs between Error, Speed, Noise, and Energy Dissipation in Biological Processes with Proofreading

2019

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“…The active participation of water is also essential for the intercalation of several drug molecules [19]. Water-mediated interactions also play a crucial role in biomolecular recognition processes, and also in kinetic proof reading [20]. Water is found in many confined geometries, even only a few nanometers in length.…”

Section: Introductionmentioning

confidence: 99%

Anomalous water dynamics at surfaces and interfaces: synergistic effects of confinement and surface interactions

Biswas

Bagchi

2017

J. Phys.: Condens. Matter

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In nature, water is often found in contact with surfaces that are extended on the scale of molecule size but small on a macroscopic scale. Examples include lipid bilayers and reverse micelles as well as biomolecules like proteins, DNA and zeolites, to name a few. While the presence of surfaces and interfaces interrupts the continuous hydrogen bond network of liquid water, confinement on a mesoscopic scale introduces new features. Even when extended on a molecular scale, natural and biological surfaces often have features (like charge, hydrophobicity) that vary on the scale of the molecular diameter of water. As a result, many new and exotic features, which are not seen in the bulk, appear in the dynamics of water close to the surface. These different behaviors bear the signature of both water-surface interactions and of confinement. In other words, the altered properties are the result of the synergistic effects of surface-water interactions and confinement. Ultrafast spectroscopy, theoretical modeling and computer simulations together form powerful synergistic approaches towards an understanding of the properties of confined water in such systems as nanocavities, reverse micelles (RMs), water inside and outside biomolecules like proteins and DNA, and also between two hydrophobic walls. We shall review the experimental results and place them in the context of theory and simulations. For water confined within RMs, we discuss the possible interference effects propagating from opposite surfaces. Similar interference is found to give rise to an effective attractive force between two hydrophobic surfaces immersed and kept fixed at a separation of d, with the force showing an exponential dependence on this distance. For protein and DNA hydration, we shall examine a multitude of timescales that arise from frustration effects due to the inherent heterogeneity of these surfaces. We pay particular attention to the role of orientational correlations and modification of the same due to interaction with the surfaces.

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“…This lacuna is indeed a source of serious problem not only in study of kinetic proof reading and enzyme kinetics but also, as we find here, in theoretical investigations of immunology. Finally, master equations involved in all such problems are solved by employing the method of mean first passage time [32] , [36] , [37] , Gillespie algorithm or straight forward numerical integration. We adopt both the deterministic approach by solving differential equations numerically and stochastic simulation by using Gillespie algorithm [38] , [39] .…”

Section: Introductionmentioning

confidence: 99%

“…Finally, master equations involved in all such problems are solved by employing the method of mean first passage time [32,36,37], Gillespie algorithm or straight forward numerical integration. We adopt both the deterministic approach by solving differential equations numerically and stochastic simulation by employing Gillespie algorithm [38,39].…”

Section: Introductionmentioning

confidence: 99%

A Stochastic Chemical Dynamic Approach to Correlate Autoimmunity and Optimal Vitamin-D Range

2014

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Motivated by several recent experimental observations that vitamin-D could interact with antigen presenting cells (APCs) and T-lymphocyte cells (T-cells) to promote and to regulate different stages of immune response, we developed a coarse grained but general kinetic model in an attempt to capture the role of vitamin-D in immunomodulatory responses. Our kinetic model, developed using the ideas of chemical network theory, leads to a system of nine coupled equations that we solve both by direct and by stochastic (Gillespie) methods. Both the analyses consistently provide detail information on the dependence of immune response to the variation of critical rate parameters. We find that although vitamin-D plays a negligible role in the initial immune response, it exerts a profound influence in the long term, especially in helping the system to achieve a new, stable steady state. The study explores the role of vitamin-D in preserving an observed bistability in the phase diagram (spanned by system parameters) of immune regulation, thus allowing the response to tolerate a wide range of pathogenic stimulation which could help in resisting autoimmune diseases. We also study how vitamin-D affects the time dependent population of dendritic cells that connect between innate and adaptive immune responses. Variations in dose dependent response of anti-inflammatory and pro-inflammatory T-cell populations to vitamin-D correlate well with recent experimental results. Our kinetic model allows for an estimation of the range of optimum level of vitamin-D required for smooth functioning of the immune system and for control of both hyper-regulation and inflammation. Most importantly, the present study reveals that an overdose or toxic level of vitamin-D or any steroid analogue could give rise to too large a tolerant response, leading to an inefficacy in adaptive immune function.

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Kinetic Proofreading at Single Molecular Level: Aminoacylation of tRNAIle and the Role of Water as an Editor

Cited by 4 publications

References 25 publications

Trade-Offs between Error, Speed, Noise, and Energy Dissipation in Biological Processes with Proofreading

Trade-Offs between Error, Speed, Noise, and Energy Dissipation in Biological Processes with Proofreading

Anomalous water dynamics at surfaces and interfaces: synergistic effects of confinement and surface interactions

A Stochastic Chemical Dynamic Approach to Correlate Autoimmunity and Optimal Vitamin-D Range

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