Power Strokes in Molecular Motors: Predictive, Irrelevant, or Somewhere in Between? DOI
Emanuele Penocchio, Geyao Gu, Alex Albaugh

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

For several decades, molecular motor directionality has been rationalized in terms of the free energy conformations visited before and after takes a step, so-called power stroke mechanism with analogues macroscopic engines. Despite theoretical experimental demonstrations its flaws, language is quite ingrained, some communities still value intuition. By building catalysis-driven into simulated numerical experiments, we here systematically report on how responds when modified accordingly to We confirm that generally does not predict directionality. Nevertheless, simulations illustrate relative stability should be included as potential design element adjust directional bias. Though strokes are formally unimportant for determining directionality, show practical attempts alter have side effects can fact The change bias align what intuition would suggested, offering explanation why flawed retain apparent utility engineering specific systems.

Language: Английский

Selective Protein (Post-)modifications through Dynamic Covalent Chemistry: Self-activated SNAr Reactions DOI
Ferran Esteve, J.‐L. Schmitt, Sergii Kolodych

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 2, 2025

SNAr reactions were remarkably accelerated using a pretargeting and activating unit based on dynamic covalent chemistry (DCvC). A Cys attack at the C–F bond aromatic ring of salicylaldehyde derivatives was only observed upon iminium formation with neighboring Lys residue model small peptides. Such self-activation ascribed to stronger electron-withdrawing capability respect that parent aldehyde stabilized transition state reaction, together higher preorganization reactive groups in cationic aldiminium species. This approach further applied for functionalization two antibodies. In both cases, presence group close proximity resulted noteworthy increase bioconjugation yields, excellent chemo-selectivity. Whereas modification an IgG1 antibody led stochastic product distributions, microenvironment selectivity noted when employing IgG4, line lower number residues hinge region latter. Additionally, postfunctionalization modified antibodies attained through exchange tethered derivative hydrazides, representing unprecedented "tag modify" selective strategy DCvC.

Language: Английский

Citations

2
Structural Influence of the Chemical Fueling System on a Catalysis-Driven Rotary Molecular Motor DOI Creative Commons

Hua‐Kui Liu,

Toufic W. Mrad, Axel Troncossi

et al.

Journal of the American Chemical Society, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Continuous directionally biased 360° rotation about a covalent single bond was recently realized in the form of chemically fueled 1-phenylpyrrole 2,2′-dicarboxylic acid rotary molecular motor. However, original fueling system and reaction conditions resulted motor directionality only ∼3:1 (i.e., on average backward for every three forward rotations), along with catalytic efficiency operation 97% fuel 14%. Here, we report efficacy series chiral carbodiimide fuels hydrolysis promoters (pyridine pyridine N-oxide derivatives) driving improved directional this motor-molecule. We outline complete network operation, composed directional, futile, slip cycles. Using derivatives where final conformational step is either very slow or completely blocked, phenylpyrrole diacid becomes enantiomerically enriched, allowing kinetic gating individual steps cycle to be measured. The that produces highest gives 13% enantiomeric excess (e.e.) anhydride-forming kinetically gated step, while most effective promoter generates 90% e.e. step. Combining best-performing into results 92% e.e.. Under dilute chemostated regime (to avoid N-acyl urea formation at high concentrations promoters), continuously rotates ∼24:1 24 rotations) >99% 51%.

Language: Английский

Citations

1
Analysis of kinetic asymmetry in a multi-cycle reaction network establishes the principles for autonomous compartmentalized molecular ratchets DOI Creative Commons
Emanuele Penocchio,

Ahmad Bachir,

Alberto Credi

et al.

Chem, Journal Year: 2024, Volume and Issue: 10(12), P. 3644 - 3655

Published: Sept. 13, 2024

Language: Английский

Citations

7
Steady-state solution of Markov jump processes in terms of arrival probabilities DOI
Diego Frezzato

Physical review. E, Journal Year: 2025, Volume and Issue: 111(1)

Published: Jan. 14, 2025

Several dynamical processes can be modeled as Markov jump among a finite number N of sites (the distinct physical states). Here we consider strongly connected networks with time-independent site-to-site rate constants, and focus on the steady-state occupation probabilities sites. We provide physically framed expression distribution in terms arrival probabilities, here defined going from starting to target given jumps (regardless time required). In particular, full set return (for all network) up N-1 is necessary sufficient. A few examples illustrate outcomes, including case stochastic chemical kinetics.

Language: Английский

Citations

0
Steady-state probabilities for Markov jump processes in terms of powers of the transition rate matrix DOI Creative Commons
Diego Frezzato

The Journal of Chemical Physics, Journal Year: 2024, Volume and Issue: 160(23)

Published: June 21, 2024

Several types of dynamics at stationarity can be described in terms a Markov jump process among finite number N representative sites. Before dealing with the dynamical aspects, one basic problem consists expressing priori steady-state occupation probabilities In particular, wishes to go beyond mere black-box computational tools and find expressions which rate constants appear explicitly, therefore allowing for potential design/control network. For strongly connected networks admitting unique stationary state all sites populated, here we express formula that involves powers transition matrix up order − 1. We also provide an expression derivatives respect constants, possibly useful sensitivity analysis frameworks. Although refer (bio)chemical thermal equilibrium or under nonequilibrium conditions, results are valid any same assumptions.

Language: Английский

Citations

2
The role of Kinetic Asymmetry in Chemical and Thermodynamic Coupling DOI
R. Dean Astumian

ChemSystemsChem, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 15, 2024

Abstract The input of energy can shift an isomerization reaction A⇌B away from equilibrium, but which way, in favor A or B? answer to this question lies understanding kinetic asymmetry, a concept first discussed the context how oscillating fluctuating perturbation act concert with catalyst drive equilibrium. key theoretical result is non‐equilibrium pumping equality that generalizes idea equilibrium constant steady‐state.

Language: Английский

Citations

1
Power Strokes in Molecular Motors: Predictive, Irrelevant, or Somewhere in Between? DOI
Emanuele Penocchio, Geyao Gu, Alex Albaugh

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 20, 2024

For several decades, molecular motor directionality has been rationalized in terms of the free energy conformations visited before and after takes a step, so-called power stroke mechanism with analogues macroscopic engines. Despite theoretical experimental demonstrations its flaws, language is quite ingrained, some communities still value intuition. By building catalysis-driven into simulated numerical experiments, we here systematically report on how responds when modified accordingly to We confirm that generally does not predict directionality. Nevertheless, simulations illustrate relative stability should be included as potential design element adjust directional bias. Though strokes are formally unimportant for determining directionality, show practical attempts alter have side effects can fact The change bias align what intuition would suggested, offering explanation why flawed retain apparent utility engineering specific systems.

Language: Английский

Citations

1