Emanuele Penocchio

Pumping molecules against a gradient without a pump?

Back-to-back with @boekhovenlab.bsky.social, we describe minimal systems that use chemical energy to transport molecules against a concentration gradient.

It started with a little shock!🧵

Us: shorturl.at/smQNF
Job's team: shorturl.at/zftps

Great opportunity to ratchet your PhD ;)

With my 5+ years of experience, I can confirm that working with Ben is fantastic!

Here is a serious candidate for my "Paper of the Year" competition 🤩

Congrats @profdaveleigh.bsky.social @stefanborsley.bsky.social @giusepponelab.bsky.social and co-workers!

Last but not least, we acknowledge that the TOC image was generated with the beta version of toddGPT, an advanced AI only available @nuchemistry.bsky.social 🤖

Importantly, by showing that the Brownian information ratchet mechanism can explain power stroke engineering experiments, we informed a long-standing debate in which those experiments have been contrasted with the theory of kinetic asymmetry. Full story in the paper ;)

Our work suggests that introducing power strokes in
chemically-driven synthetic molecular motors might affect their directional bias, thus providing a practical way to alter kinetic asymmetry in Brownian information ratchets that was previously overlooked.

The change in the bias can align with what power stroke intuition would have suggested, offering a potential explanation for why the flawed power stroke mechanism can retain apparent utility when engineering directionality in specific systems.

We found a resolution perfectly consistent with the Brownian ratchet mechanism: though power strokes are formally unimportant for determining directionality, we explicitly show that practical attempts to alter a power stroke have side effects that can change the directional bias.

Here is a conundrum: chemical reaction network theory proved power strokes irrelevant for predicting molecular motor directionality. However, power strokes seem widespread in biology, and some have claimed they can tune biomotor directionality by changing power stroke magnitude 🤔

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

If you've ever read about molecular motors, you've probably wondered about "power strokes." We looked into that by simulating a catalysis-driven molecular motor explicitly 🧐

I am super happy to share my latest work with Alex, Geyao, and Todd @nuchemistry.bsky.social

pubs.acs.org/doi/10.1021/...

PhD alert! I have two ERC-funded PhD positions to uncover the chemical origins of life (Oct 2025). *UK fees only*. Projects described here: www.lclu.cam.ac.uk/studentship-...
Email me if interested - deadline (PhD in Biochemistry, Uni of Cambridge): Jan 7th!
Please share within your networks!

Analysis of kinetic asymmetry in a multi-cycle reaction network establishes the principles for autonomous compartmentalized molecular ratchets Kinetic asymmetry is a key parameter describing non-equilibrium systems: it indicates the directionality of a reaction network under steady-state cond…

They spoil the main results of our recent Chem paper, where we show how to deal with multiple cycles and spatial separation for driven chemical reaction networks.

Here is the full paper: www.sciencedirect.com/science/arti...

@giuliosflask.bsky.social @deanast.bsky.social

Out-of-equilibrium compartments: Thinking inside the box Biological cells sustain an out-of-equilibrium state by harnessing energy flows across compartment boundaries. In this issue of Chem, Penocchio et al.…

Looking for a #systemschemistry theory "starter pack"? ;)

The fantastic Preview by @profdaveleigh.bsky.social James, and Joaquin is the perfect excuse for throwing my first post in the blue sky!

www.sciencedirect.com/science/arti...