scholarly journals Dissecting the energetics of subunit rotation in the ribosome

2019 ◽  
Author(s):  
Mariana Levi ◽  
Paul C. Whitford
Keyword(s):  
Free Energy ◽  
Transition State ◽  
Energy Barrier ◽  
Small Subunit ◽  
Free Energy Barrier ◽  
Accurate Expression ◽  
State Ensemble ◽  
Subunit Rotation ◽  
Transition State Ensemble

AbstractThe accurate expression of proteins requires the ribosome to efficiently undergo elaborate conformational rearrangements. The most dramatic of these motions is subunit rotation, which is necessary for tRNA molecules to transition between ribosomal binding sites. While rigid-body descriptions provide a qualitative picture of the process, obtaining quantitative mechanistic insights requires one to account for the relationship between molecular flexibility and collective dynamics. Using simulated rotation events, we assess the quality of experimentally-accessible measures for describing the collective displacement of the ~ 4000-residue small subunit. For this, we ask whether each coordinate is able to identify the underlying free-energy barrier and transition state ensemble (TSE). We find that intuitive structurally-motivated coordinates (e.g. rotation angle, inter-protein distances) can distinguish between the endpoints, though they are poor indicators of barrier-crossing events, and they underestimate the free-energy barrier. In contrast, coordinates based on inter-subunit bridges can identify the TSE. We additionally verify that the committor probability for the putative TSE configurations is 0.5, a hallmark feature of any transition state. In terms of structural properties, these calculations implicate a transition state in which flexibility allows for asynchronous rearrangements of the bridges as the ribosome adopts a partially-rotated orientation. These calculations provide a theoretical foundation, upon which experimental techniques may precisely quantify the energy landscape of the ribosome.

scholarly journals The Dynamics of Subunit Rotation in a Eukaryotic Ribosome

Biophysica ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 204-221
Author(s):  
Frederico Campos Freitas ◽  
Gabriele Fuchs ◽  
Ronaldo Junio de Oliveira ◽  
Paul Charles Whitford
Keyword(s):  
Free Energy ◽  
Large Scale ◽  
Small Subunit ◽  
Free Energy Barrier ◽  
Temperature Dependent ◽  
Molecular Flexibility ◽  
Subunit Rotation ◽  
Biological Kinetics ◽  
Rate Limiting ◽  
Reversible Rotation

Protein synthesis by the ribosome is coordinated by an intricate series of large-scale conformational rearrangements. Structural studies can provide information about long-lived states, however biological kinetics are controlled by the intervening free-energy barriers. While there has been progress describing the energy landscapes of bacterial ribosomes, very little is known about the energetics of large-scale rearrangements in eukaryotic systems. To address this topic, we constructed an all-atom model with simplified energetics and performed simulations of subunit rotation in the yeast ribosome. In these simulations, the small subunit (SSU; ∼1 MDa) undergoes spontaneous and reversible rotation events (∼8∘). By enabling the simulation of this rearrangement under equilibrium conditions, these calculations provide initial insights into the molecular factors that control dynamics in eukaryotic ribosomes. Through this, we are able to identify specific inter-subunit interactions that have a pronounced influence on the rate-limiting free-energy barrier. We also show that, as a result of changes in molecular flexibility, the thermodynamic balance between the rotated and unrotated states is temperature-dependent. This effect may be interpreted in terms of differential molecular flexibility within the rotated and unrotated states. Together, these calculations provide a foundation, upon which the field may begin to dissect the energetics of these complex molecular machines.

Elucidating the role of solvents in acid catalyzed dehydration of biorenewable hydroxy-lactones

2020 ◽  
Vol 5 (4) ◽  
pp. 651-662 ◽  
Author(s):  
Gourav Shrivastav ◽  
Tuhin S. Khan ◽  
Manish Agarwal ◽  
M. Ali Haider
Keyword(s):  
Free Energy ◽  
Transition State ◽  
Energy Barrier ◽  
Free Energy Barrier ◽  
Activation Free Energy ◽  
Acid Catalyzed

Utilizing the differential stabilization of reactant and transition state in the polar and apolar solvents to lower the activation free energy barrier for acid-catalyzed dehydration of hydroxy lactones.

scholarly journals Sampling the Folding Transition State Ensemble in a Tube-Like Model of Protein

10.29007/ml3c ◽  
2020 ◽  
Author(s):  
Ba Hung Nguyen ◽  
Hoang Trinh Xuan
Keyword(s):  
Free Energy ◽  
Transition State ◽  
Energy Surface ◽  
Sampling Technique ◽  
Small Region ◽  
Umbrella Sampling ◽  
Free Energy Surface ◽  
State Ensemble ◽  
State Region ◽  
Transition State Ensemble

We used the tube model with Go-like potential for native contacts to study the folding transition of a designed three-helix bundle and a designed protein G-like structure. It is shown that both proteins in this model are two-state folders with a cooperative folding transition coincided with the collapse transition. We defined the transition states as protein conformations in a small region around the saddle point on a free energy surface with the energy and the conformational root-mean-square deviation (RMSD) from the native state as the coordinates. The transition state region on the free energy surface then was sampled by using the umbrella sampling technique. We show that the transition state ensemble is broad consisting of different conformations that have different folded and unfolded elements.

scholarly journals Sampling the Folding Transition State Ensemble in a Tube-like Model of Protein

2019 ◽  
Vol 29 (2) ◽  
pp. 129
Author(s):  
Nguyen Ba Hung ◽  
Trinh Xuan Hoang
Keyword(s):  
Free Energy ◽  
Transition State ◽  
Energy Surface ◽  
Sampling Technique ◽  
Small Region ◽  
Umbrella Sampling ◽  
Free Energy Surface ◽  
State Ensemble ◽  
State Region ◽  
Transition State Ensemble

We used the tube model with Go-like potential for native contacts to study the folding transition of a designed three-helix bundle and a designed protein G-like structure. It is shown that both proteins in this model are two-state folders with a cooperative folding transition coincided with the collapse transition. We defined the transition states as protein conformations in a small region around the saddle point on a free energy surface with the energy and the conformationalroot mean square deviation (rmsd) from the native state as the coordinates. The transition state region on the free energy surface then was sampled by using umbrella sampling technique. We show that the transition state ensemble is broad consisting of different conformations that have different folded and unfolded elements.

scholarly journals The dynamics of subunit rotation in a eukaryotic ribosome

2021 ◽  
Author(s):  
Frederico Campos Freitas ◽  
Gabriele Fuchs ◽  
Ronaldo Junio de Oliveira ◽  
Paul Charles Whitford
Keyword(s):  
Free Energy ◽  
Large Scale ◽  
Small Subunit ◽  
Free Energy Barrier ◽  
Temperature Dependent ◽  
Molecular Flexibility ◽  
Subunit Rotation ◽  
Conformational Rearrangements ◽  
Biological Kinetics ◽  
Rate Limiting

AbstractProtein synthesis by the ribosome is coordinated by an intricate series of large-scale conformational rearrangements. Structural studies can provide information about long-lived states, however biological kinetics are controlled by the intervening free-energy barriers. While there has been progress describing the energy landscapes of bacterial ribosomes, very little is known about the energetics of large-scale rearrangements in eukaryotic systems. To address this topic, we constructed an all-atom model with simplified energetics and performed simulations of subunit rotation in the yeast ribosome. In these simulations, the small subunit (SSU; ~1MDa) undergoes spontaneous and reversible rotations (~ 8°). By enabling the simulation of this rearrangement under equilibrium conditions, these calculations provide initial insights into the molecular factors that control dynamics in eukaryotic ribosomes. Through this, we are able to identify specific inter-subunit interactions that have a pronounced influence on the rate-limiting free-energy barrier. We also show that, as a result of changes in molecular flexibility, the thermodynamic balance between the rotated and unrotated states is temperature-dependent. This effect may be interpreted in terms of differential molecular flexibility within the rotated and unrotated states. Together, these calculations provide a foundation, upon which the field may begin to dissect the energetics of these complex molecular machines.

The experimental survey of protein-folding energy landscapes

2005 ◽  
Vol 38 (3) ◽  
pp. 245-288 ◽  
Author(s):  
Mikael Oliveberg ◽  
Peter G. Wolynes
Keyword(s):  
Free Energy ◽  
Protein Folding ◽  
Transition State ◽  
Energy Landscape ◽  
Energy Profile ◽  
Global Features ◽  
Value Analysis ◽  
Free Energy Profile ◽  
State Ensemble ◽  
Transition State Ensemble

1. Introduction 22. The macroscopic and microscopic views of protein folding 22.1 The macroscopic view: the experimental folding free-energy profile 22.2 The microscopic view: an underlying energy landscape 33. The micro to macro projection: from an energy landscape to a free-energy profile 64. Global features of the protein folding transition-state ensemble 124.1 Overall transition state location β[Dagger]: a measure of compactness 124.2 What makes folding so robust ? 135. Structural characterization of the transition-state ensemble 165.1 Insights from ϕ-value analysis 166. Deviations from ideality 206.1 β[Dagger] shifts along seemingly robust trajectories 216.2 Anomalous ϕ values, frustration and inhomogeneities 257. Intermediates 288. Detours, traps and frustration 298.1 Premature collapse and non-native trapping 299. Diffusion on the energy landscape and the elementary events of protein folding 3010. Malleability of folding routes: changes of the dominant collective coordinates for folding 3311. The evolution of the shape of the energy landscape 3511.1 Negative design: the hidden dimension of the folding code 3512. Mechanistic multiplicity and evolutionary choice 3613. Acknowledgements 3714. References 38We review what has been learned about the protein-folding problem from experimental kinetic studies. These studies reveal patterns of both great richness and surprising simplicity. The patterns can be interpreted in terms of proteins possessing an energy landscape which is largely, but not completely, funnel-like. Issues such as speed limitations of folding, the robustness of folding, the origin of barriers and cooperativity and the ensemble nature of transition states, intermediate and traps are assessed using the results from several experimental groups highlighting energy-landscape ideas as an interpretive framework.

Exploring structures in protein folding funnels with free energy functionals: the transition state ensemble

1999 ◽  
Vol 287 (3) ◽  
pp. 675-694 ◽  
Author(s):  
Benjamin A. Shoemaker ◽  
Jin Wang ◽  
Peter G. Wolynes
Keyword(s):  
Free Energy ◽  
Protein Folding ◽  
Transition State ◽  
Energy Functionals ◽  
State Ensemble ◽  
Transition State Ensemble

DFT study on the hydrolysis of metsulfuron-methyl: A sulfonylurea herbicide

2018 ◽  
Vol 17 (08) ◽  
pp. 1850050 ◽  
Author(s):  
Qiuhan Luo ◽  
Gang Li ◽  
Junping Xiao ◽  
Chunhui Yin ◽  
Yahui He ◽  
...  
Keyword(s):  
Free Energy ◽  
Water Molecule ◽  
Carbonyl Group ◽  
Energy Barrier ◽  
Density Functional ◽  
Free Energy Barrier ◽  
Functional Theory ◽  
Metsulfuron Methyl ◽  
Catalytic Role ◽  
Hydrolysis Of

Sulfonylureas are an important group of herbicides widely used for a range of weeds and grasses control particularly in cereals. However, some of them tend to persist for years in environments. Hydrolysis is the primary pathway for their degradation. To understand the hydrolysis behavior of sulfonylurea herbicides, the hydrolysis mechanism of metsulfuron-methyl, a typical sulfonylurea, was investigated using density functional theory (DFT) at the B3LYP/6-31[Formula: see text]G(d,p) level. The hydrolysis of metsulfuron-methyl resembles nucleophilic substitution by a water molecule attacking the carbonyl group from aryl side (pathway a) or from heterocycle side (pathway b). In the direct hydrolysis, the carbonyl group is directly attacked by one water molecule to form benzene sulfonamide or heterocyclic amine; the free energy barrier is about 52–58[Formula: see text]kcal[Formula: see text]mol[Formula: see text]. In the autocatalytic hydrolysis, with the second water molecule acting as a catalyst, the free energy barrier, which is about 43–45[Formula: see text]kcal[Formula: see text]mol[Formula: see text], is remarkably reduced by about 11[Formula: see text]kcal[Formula: see text]mol[Formula: see text]. It is obvious that water molecules play a significant catalytic role during the hydrolysis of sulfonylureas.

scholarly journals Effect of free energy barrier on pattern transition in 2D diffusion limited aggregation morphology of electrodeposited copper

Heliyon ◽  
2018 ◽  
Vol 4 (12) ◽  
pp. e01022
Author(s):  
Souradeep Ghosh ◽  
Raveena Gupta ◽  
Subhankar Ghosh
Keyword(s):  
Free Energy ◽  
Energy Barrier ◽  
Free Energy Barrier ◽  
Diffusion Limited Aggregation ◽  
Diffusion Limited

Degree of pyramidality governs the height and peak position of the free-energy-barrier for the cis–trans isomerization of N-Methylacetamide

2011 ◽  
Vol 503 (1-3) ◽  
pp. 139-144 ◽  
Author(s):  
Yasushige Yonezawa ◽  
Daron M. Standley ◽  
Haruki Nakamura
Keyword(s):  
Free Energy ◽  
Energy Barrier ◽  
Peak Position ◽  
Free Energy Barrier ◽  
Trans Isomerization
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