Theoretical study of a proton wire mechanism for the peptide bond formation in the ribosome

Acosta-Silva, Carles; Bertrán, Juan; Branchadell, Vicenç; Oliva, A.

doi:10.1007/s00214-017-2066-2

Cited by 3 publications

(5 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 1280 − 1282 Finally, Ehrenberg and co-workers explained the different pH-sensitivities of peptidyl transfer involving various A-site aminoacyl-tRNAs as correlated with the distinct p K a shifts of their α-amino groups under conditions where reaction chemistry is rate-limiting. 1285 Note that the peptidyl-transferase center has been studied also by pure QM approaches, for example, in ref ( 1286 ).…”

Section: Simulations Of Specific Rna Systemsmentioning

confidence: 99%

“…This entropy reduction was found to be associated primarily with a reduction in the necessary solvent reorganization rather than with conformational alignment of the substrates. − Finally, Ehrenberg and co-workers explained the different pH-sensitivities of peptidyl transfer involving various A-site aminoacyl-tRNAs as correlated with the distinct p K a shifts of their α-amino groups under conditions where reaction chemistry is rate-limiting . Note that the peptidyl-transferase center has been studied also by pure QM approaches, for example, in ref .…”

Section: Simulations Of Specific Rna Systemsmentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2018

View full text Add to dashboard Cite

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.

show abstract

Section: Simulations Of Specific Rna Systemsmentioning

confidence: 99%

Section: Simulations Of Specific Rna Systemsmentioning

confidence: 99%

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

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Although the role of the 2′-OH group of A76 of peptidyl-tRNA is debatable, [33][34][35][36][37] we adopted a substrate-assisted catalysis model in which the 2′-OH group of A76 catalyzes peptide bond formation, 37) since this is consistent with experimental data and calculated models from previous mechanistic studies. 8,9,[12][13][14][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]33,34) The optimized geometries of TS1 and TS2 are shown in Fig. 3.…”

Section: Resultsmentioning

confidence: 99%

“…Although this is inconsistent with the results of kinetic studies showing that the formation of the tetrahedral intermediate is rate-limiting, 8) a similar trend has been reported in theoretical calcula-tions of stepwise amide or peptide bond formation. [10][11][12][13][20][21][22][23][24][25][26][27][29][30][31] According to Rangelov et al, the height of the energy barrier of peptide bond formation is related to the angular deviation of the proton transfer route (O2′-H-O3′ or N-H-O2′) from linearity in the transition state. 12) Therefore, the larger angular deviation of Δθ O2′-H-O3′ = 47.5° at TS2 compared to that of Δθ N-H-O2′ = 20.3° at TS1 supports our conclusion that the ratelimiting step is TS2.…”

Section: Resultsmentioning

confidence: 99%

“…18) Quantum chemical calculations have been used to study both stepwise and concerted mechanisms. [20][21][22][23][24][25][26][27][28][29][30][31] In one study of systems containing 44-56 atoms of the PTC analyzed using the M06-2X/6-311 + G(d,p) level of theory, C-N bond formation and C-O bond cleavage were accompanied by proton transfer of the NH 2 group, 2′-OH group of A76, and water molecules in the transition states (proton-shuttle mechanism); these authors showed that a stepwise reaction was favored over a concerted one and that the 2′-OH group of rRNA A2451 in the active site of the ribosome stabilized the transition states through hydrogen bonding. 22) In a previous study, we demonstrated the stepwise mechanism of the peptidyl transfer reaction in a ribosome system consisting of 2354 atoms using the ONIOM method 23) (Fig.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Theoretical Study of the Mechanism of Ribosomal Peptide Bond Formation Using the ONIOM Method

Fukushima

Esaki

2021

Chem. Pharm. Bull.

View full text Add to dashboard Cite

Peptide bond formation in living cells occurs at the peptidyl transferase center (PTC) of the large ribosomal subunit and involves the transfer of the peptidyl group from peptidyl-tRNA to aminoacyl-tRNA. Despite numerous kinetic and theoretical studies, many details of this reaction -such as whether it proceeds via a stepwise or concerted mechanism-remain unclear. In this study, we calculated the geometry and energy of the transition states and intermediates in peptide bond formation in the PTC environment using the ONIOM (our own n-layered integrated molecular orbital and molecular mechanics) method. The calculations indicated that the energy of the transition states of stepwise mechanisms are lower than those of concerted mechanisms and suggested that the reaction involves a neutral tetrahedral intermediate that is stabilized through the hydrogen-bonding network in the PTC environment. The results will lead to a better understanding of the mechanism of peptidyl transfer reaction, and resolve fundamental questions of the steps and molecular intermediates involved in peptide bond formation in the ribosome.

show abstract

Quantum mechanical tunnelling through the catalytic effects of A2451 ribosomal residue during a stepwise peptide bond formation

Monajemi

Zain

Ishida

et al. 2019

Biochem. Cell Biol.

View full text Add to dashboard Cite

The search for the mechanism of ribosomal peptide bond formation is still ongoing. Even though the actual mechanism of peptide bod formation is still unknown, the dominance of proton transfer in this reaction is known for certain. Therefore, it is vital to take the quantum mechanical effects on proton transfer reaction into consideration; the effects of which were neglected in all previous studies. In this study, we have taken such effects into consideration using a semi-classical approach to the overall reaction mechanism. The M06-2X density functional with the 6-31++G(d,p) basis set was used to calculate the energies of the critical points on the potential energy surface of the reaction mechanism, which are then used in transition state theory to calculate the classical reaction rate. The tunnelling contribution is then added to the classical part by calculating the transmission permeability and tunnelling constant of the reaction barrier, using the numerical integration over the Boltzmann distribution for the symmetrical Eckart potential. The results of this study, which accounts for quantum effects, indicates that the A2451 ribosomal residue induces proton tunnelling in a stepwise peptide bond formation.

show abstract

Theoretical study of a proton wire mechanism for the peptide bond formation in the ribosome

Cited by 3 publications

References 39 publications

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

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

Theoretical Study of the Mechanism of Ribosomal Peptide Bond Formation Using the ONIOM Method

Quantum mechanical tunnelling through the catalytic effects of A2451 ribosomal residue during a stepwise peptide bond formation

Contact Info

Product

Resources

About