Brownian dynamics study of the association between the 70S ribosome and elongation factor G

Długosz, Maciej; Huber, Gary L.; McCammon, J. Andrew; Trylska, Joanna

doi:10.1002/bip.21619

Cited by 20 publications

(17 citation statements)

References 109 publications

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“… 987 BD has also been used to study association of elongation factor G with the ribosome. 986 These BD calculations demonstrate that diverse computational approaches can complement each other in studies on various aspects of the ribosome’s function.…”

Section: Simulations Of Specific Rna Systemsmentioning

confidence: 91%

“…BD simulations were also used to study the kinetics and association of paromomycin to the entire 30S ribosomal subunit. 986 The resulting model suggested that specific binding at the ribosomal A-site starts with nonspecific antibiotic diffusion toward the 30S subunit and is followed by exploration of the subunit’s surface. 977 The calculations did not suggest any specific long-range electrostatic navigation through the landscape to the A-site, but identified two entrances to the A-site around which the mobility of paromomycin is high.…”

Section: Simulations Of Specific Rna Systemsmentioning

confidence: 99%

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RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

et al. 2018

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With both catalytic and genetic functions, ribonucleic acid (RNA) is perhaps the most pluripotent chemical species in molecular biology, and its functions are intimately linked to its structure and dynamics. Computer simulations, and in particular atomistic molecular dynamics (MD), allow structural dynamics of biomolecular systems to be investigated with unprecedented temporal and spatial resolution. We here provide a comprehensive overview of the fast-developing field of MD simulations of RNA molecules. We begin with an in-depth, evaluatory coverage of the most fundamental methodological challenges that set the basis for the future development of the field, in particular, the current developments and inherent physical limitations of the atomistic force fields and the recent advances in a broad spectrum of enhanced sampling methods. We also survey the closely related field of coarse-grained modeling of RNA systems. After dealing with the methodological aspects, we provide an exhaustive overview of the available RNA simulation literature, ranging from studies of the smallest RNA oligonucleotides to investigations of the entire ribosome. Our review encompasses tetranucleotides, tetraloops, a number of small RNA motifs, A-helix RNA, kissing-loop complexes, the TAR RNA element, the decoding center and other important regions of the ribosome, as well as assorted others systems. Extended sections are devoted to RNA–ion interactions, ribozymes, riboswitches, and protein/RNA complexes. Our overview is written for as broad of an audience as possible, aiming to provide a much-needed interdisciplinary bridge between computation and experiment, together with a perspective on the future of the field.

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Section: Simulations Of Specific Rna Systemsmentioning

confidence: 91%

Section: Simulations Of Specific Rna Systemsmentioning

confidence: 99%

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

et al. 2018

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“…first provided evidence for electrostatic steering using Brownian dynamics. Subsequently a number of simulation studies have observed electrostatic steering during productive complex formation in protein–protein association. Aided by Brownian dynamics simulations, the kinetic mechanism of protein association is now a mature field.…”

Section: Introductionmentioning

confidence: 99%

Protein–protein association rates captured in a single geometric parameter

Das

Basu

2015

Proteins

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Understanding factors that drive protein-protein association is of fundamental importance. We show that a single geometric parameter in crystal structures of protein-protein complexes, the angle between the electric dipole of one subunit and the partner-generated electric field at the same subunit, linearly correlates with experimentally determined protein-protein association rates. Imprint of a dynamic kinetic process in a single static geometric parameter, associated with mutual electrostatic orientation of subunits in protein-protein complexes, is elegant and demonstrates the universality of electrostatic steering in attenuating protein-protein association rates. That the essence of a complex phenomenon could be captured by properties of the final crystal structure of the complex implies that the electrostatic orientations of protein subunits in crystal structures and the associated transition states are nearly identical. Further, the cosine of the angle, alone, is shown to be sufficient in predicting association rate constants, with accuracies comparable to currently available predictors that use more intricate methodologies. Our results offer mechanistic insights and could be useful in development of coarse-grained models.

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“…This method so far cannot provide kinetic information of binding. On the other hand, Brownian dynamic simulation, and a more recently developed method based on transient‐complex theory give promising results on predicting kinetic rates of protein association. However, the extension of these methods to membrane protein association is currently under development.…”

Section: Introductionmentioning

confidence: 99%

Linking 3D and 2D binding kinetics of membrane proteins by multiscale simulations

Xie

Chen

2014

Protein Science

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Membrane proteins are among the most functionally important proteins in cells. Unlike soluble proteins, they only possess two translational degrees of freedom on cell surfaces, and experience significant constraints on their rotations. As a result, it is currently challenging to characterize the in situ binding of membrane proteins. Using the membrane receptors CD2 and CD58 as a testing system, we developed a multiscale simulation framework to study the differences of protein binding kinetics between 3D and 2D environments. The association and dissociation processes were implemented by a coarse-grained Monte-Carlo algorithm, while the dynamic properties of proteins diffusing on lipid bilayer were captured from all-atom molecular dynamic simulations. Our simulations show that molecular diffusion, linker flexibility and membrane fluctuations are important factors in adjusting binding kinetics. Moreover, by calibrating simulation parameters to the measurements of 3D binding, we derived the 2D binding constant which is quantitatively consistent with the experimental data, indicating that the method is able to capture the difference between 3D and 2D binding environments. Finally, we found that the 2D dissociation between CD2 and CD58 is about 100-fold slower than the 3D dissociation. In summary, our simulation framework offered a generic approach to study binding mechanisms of membrane proteins.

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Brownian dynamics study of the association between the 70S ribosome and elongation factor G

Cited by 20 publications

References 109 publications

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

RNA Structural Dynamics As Captured by Molecular Simulations: A Comprehensive Overview

Protein–protein association rates captured in a single geometric parameter

Linking 3D and 2D binding kinetics of membrane proteins by multiscale simulations

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