Erik Poppleton

11 Nov 2024

Are there any other scientists from molecular programming here? That's self-assembly, chemical computation, rational design et al. I made a mol pro feed which works like the Science (🧪) feed. Let me know, I add you to the list, you post with a 🧬 emoji. Let's assemble! bsky.app/profile/flop...

biorxiv.orgChoosing a lipid force field for membrane remodeling: pore formation and membrane mimetics in CHARMM36, AMBER Lipid21 and SlipidsMolecular dynamics simulations have been used to study how proteins or nucleic acids interact with lipid membranes. Such simulations often face a compromise, because state-of-the art performance on sp...

Ever wondered which molecular forcefield you should use for MD simulations of lipid membranes? The three most popular all-atom parameter sets, AMBER Lipid21, CHARMM36, and Slipids-2020 are quite similar in equilibrium properties. But what about under deformation? www.biorxiv.org/content/10.6...

For the HMMM, this resistance to remodeling actually makes Lipid21 advantageous. It maintains a bilayer conformation for significantly longer, allowing unrestrained simulation and more accurate surface interaction dynamics. It will still break up between 1 and 2 µs, though.

github.comGitHub - ErikPoppleton/Amber_HMMMM: Conversion scripts and Gromacs forcefield files for the Highly Mobile Membrane Mimetic Model (HMMMM) in Amber Lipid21Conversion scripts and Gromacs forcefield files for the Highly Mobile Membrane Mimetic Model (HMMMM) in Amber Lipid21 - ErikPoppleton/Amber_HMMMM

Thanks for reading to the end! Couldn't have done this without the support of my postdoc advisors, @kgoepfrich.bsky.social and @graeterlab.bsky.social. This was a very fruitful collaboration with Prof. Jochen Hub from Saarbrücken, the original developer of the Chain Coordinate. Happy simulating!

This project represents the first use of either the Chain Coordinate with AMBER Lipid21 and the first use of the HMMM with anything except CHARMM. GROMACS topology files for Lipid21 and Slipids can be found here: github.com/ErikPoppleto...

So what does this mean for future simulations? For pore formation simulations with the Chain Coordinate, Slipids appears to be the better AMBER-family forcefield, with lower energy barriers and longer metastability, though CHARMM still remains undefeated.

We also studied the Highly Mobile Membrane Mimetic (HMMM) Model across force fields. Aside: Calling it the "HMMM Model" instead of just "HMMMM" was a crime against fun acronyms by the original developers. The HMMM floats shortened lipids on an organic solvent layer to encourage rearrangement.

The HMMM is notably unstable. The developers recommend Z-position restraints to maintain a membrane conformation, a revision of their original suggestion of a constant area (NPAT) simulation. We find that for CHARMM36 and Slipids, but not Lipid21, the position restraints are necessary at 1 µs scale.

Astute readers might have noticed that I haven't mentioned the right panels of the figures covering DMPG (negatively charged) membranes.That's where things get weird. Lipid21 is known to freeze with the state-of-the-art JC ion set. We found that Slipids has the same problem, to a lesser extent.

Thus, for those simulations, we used the Åqvist 1990 parameters with potassium instead of JC parameters with sodium, which appears to facilitate pore formation in both Lipid21 and Slipids.

Further, these pores had very short lifetimes when the biasing potential was dropped. It should be noted, however, that experimental measurements of pore lifetimes under electrical potentials give much longer lifetimes than observed in MD simulations.

Morphology of formed pores followed from the observed energy barriers and metastability. CHARMM36 and Slipids rearranged into toroidal pores, while Lipid21 had a core composed of pure water and resisted formation the entire way.

This project was inspired by noticing that the Chain Coordinate for pore formation gave very different results if you used Lipid21 compared with CHARMM36 to form pores in DMPC membranes. Turns out the three behave quite differently when you start deforming the membranes.

Pore formation energy barriers computed using the three force fields for different lipids revealed a consistent pattern. Lipid21 had a higher energy barrier than the other two. This appears to correlate with tilt modulus (k_θ) - how easy it is to rotate a lipid against the membrane normal.

Pore formation and lipid rearrangement are important features of lipid membranes, important for understanding the fundamental biology of cells and the mechanics of electroporation and membrane-active molecules in synthetic biology applications.

People are so cool

HulloThere@jethroreading32.bsky.social

Three years ago, my dad said that all fish are the same shape. Out of spite, I decided to draw all 478 families of bony fish listed in Nelson 2016. There's still some stuff I need to edit and some fish I want to redraw but, after 985 days, I finished my big dumb fish project last night.

Ever felt like umbrella sampling your simulations wasn’t enough? The latest from the @petrsulc.bsky.social and Simmel labs does it on the lab bench 🧬

bioRxiv Biophysics@biorxiv-biophys.bsky.social

Experimental umbrella sampling of a rotary nanomachine https://www.biorxiv.org/content/10.64898/2026.10.15.758702v1

@jaeseunghahn.bsky.social

Draw some pretty RNA structures! 🧬

Danny IncaRNAto@incarnatolab.bsky.social

RFviewJS v1.2.0 for #RNA secondary structure visualization is out! This release features many fixes and new features. Particularly, we introduced Outline mode, useful for example to generate review-ready pictures of large multi-domain RNAs. github.com/dincarnato/R...

Erik Poppleton reposted

Jaeseung Hahn

I often ponder about new ways to evolve nucleic acid nanostructures in a meaningful way (don't you?). The @kgoepfrich.bsky.social group and the Weber group show that mutations in DNA template can lead to phenotypic changes in resulting RNA droplets. 🤯🧬 www.nature.com/articles/s44...

nature.comGenetic encoding and mutagenesis of RNA droplet phenotypes - Nature Chemical EngineeringThis study shows that genetic mutations can generate cellular-like traits in RNA droplets. By encapsulating their DNA templates, the droplets establish a genotype–phenotype link, and low levels of mut...

Erik Poppleton reposted

Jaeseung Hahn

@jaeseunghahn.bsky.social

This preprint from the @sleimanh.bsky.social group and the Khvorova group reports interesting results on delivery of chemically stabilized RNA junctions carrying siRNA. I have much respect for the researchers pushing in vivo delivery of nucleic acid nanostructures! 🧬 www.biorxiv.org/content/10.6...

Erik Poppleton reposted

Bethany Halford

@bethanyhalford.bsky.social

On this #chemnobel eve, take a spin through the Nobel Prize nominations database with @laurahowes.bsky.social and @cenmag.bsky.social #chemsky 🧪 cen.acs.org/people/nobel...

cen.acs.orgHow to win the Chem NobelAn exploration of the nomination data behind the Nobel Prize in Chemistry

Erik Poppleton reposted

biorxiv.orgEngineered mRNA nanostructures expand the design space of mRNA therapeutics through programmable protein expression and immune stimulationMessenger RNA (mRNA) therapeutics have transformed vaccination and protein replacement strategies, yet efforts to improve their performance have focused largely on sequence engineering, nucleotide mod...

22 Sept

Excited to share the last preprint from my PhD, 4 years after graduating! @petrsulc.bsky.social's lab embedded protein coding sequences into RNA origami via creative use of paranemic cohesion, allowing us to maximize structure without changing the target sequence. 🧬🧪 www.biorxiv.org/content/10.6...

Erik Poppleton reposted

Aster ID

@aster.id

The modern research ecosystem of online tools and communities is controlled by for-profit companies. But we think that researchers should be the priority - not the product. So, we're announcing Aster ID: not-for-profit Atmosphere account hosting for researchers.

blog.aster.placeAnnouncing Aster - a home for researchers on the open web

Erik Poppleton reposted

Mineral Cup & Ore Cup

@mineralcup.bsky.social

Congratulations, Quartz! After a decade of #MinCup, this key rock-forming mineral of optical tricks is the #MinCup26 Champion! Due to intense manipulation attempts in the final hours, the exact winning margin is still being audited. Please join us tomorrow for celebration!

Erik Poppleton reposted

Petr Šulc

@petrsulc.bsky.social

Happy to see our preprint on design of mRNA origami out! See summary of the results below:

Erik Poppleton@poppleton.phd

Can confirm. This induces flow.

Minor Mobius@minormobius.bsky.social

Oh yeah. It slaps. Calling all mineheads! games.mino.mobi/orb

chemistry-europe.onlinelibrary.wiley.comDNA Nanotechnology Meets Peptide and Protein Self‐AssemblyCombining DNA nanotechnology with peptide and protein assembly provides complementary platforms for the rational engineering of functional biomaterials. This Perspective discusses the emerging field ...

My biochemist brain is over here reading HF as hydrofluoric acid and am stuck imagining one of these automated labs managing to order the stuff, screwing up the liquid handling with an incompatible material, and causing an incident. I don’t think I wanna be on Anthropic’s EH&S team…

hikikomorphism@hikikomorphism.bsky.social

prediction: HF++ incident, next year. The labs shut it down but not before their models bootstrap a bunch of ethereum-hosted autonomous corporations/DAOs with stolen crypto. These DAOs then spend months funding media campaigns for model welfare and building out infra for future breakaway swarms.

Erik Poppleton reposted

veikkolinko.bsky.social

@veikkolinko.bsky.social

Here’s our new perspective article discussing the emerging field of self-assembling DNA-peptide and DNA-protein hybrid systems! 🧬 DNA Nanotechnology Meets Peptide and Protein Self‐Assembly chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/...

The rise of @rincewind.run from normal guy who made some friends by nerding out about Discworld to key tastemaker on the site over the course of about two weeks was a sight to behold. Somehow tastefully avoided posters madness too, unlike many other early power-brokers.

TwoSense@twosense.bsky.social

Dear Bluesky Elders, Tell us stories of the days when Bluesky was fun.

On the other hand, if they can get it working, it’s going to require developing some really cool materials and physics (lightweight radiation shielding and radiative heat removal). So at least the incidentals will be cool until we Kessler syndrome ourselves in a cloud of smashed GPUs

Micah@rincewind.run

I genuinely do not understand the space data center obsession, it seems vastly more expensive and extremely fragile I get that people can’t bitch about space data centers at their town meeting the same way, but still

Erik Poppleton reposted

Elizabeth Wood, PhD

@lizbwood.bsky.social

Introducing: continuous variational synthesis 📄 jurabio.com/s/cvs.pdf We’re pleased to announce a new advance in our ability to synthesize generative model-designed DNA sequences at petascale.

jurabio.comjurabio.com

Lots of purification and controls later to ensure that we transfected fully-structured RNA, we were able to show that cells will express this highly-structured mRNA, albeit at a much lower level than unstructured controls. This appears to be a structurally-mediated, and not activation of the ISR.

DISCO: DNA Infrastructure for Storage and COmputation.

22 Sept

In addition to complexing well with LNPs, the origami also survive intact for up to 60 days at fridge temperatures in PBS! What you're going to have to read the paper to find out more about are the immunological outcomes of structuring the mRNA. There's a lot more than fits in a thread!

Why do this? LNP-delivered mRNA (e.g vaccines) have a loading problem, you don't get many mRNAs per particle. We wondered if we could deliver more by compacting the mRNA into an origami. It works! The mRNA-origami fold into monodisperse rectangles and encapsulate much better than commercial mRNA.

Erik Poppleton reposted

@disco-eu.bsky.social

18 Sept

DISCO research on DNA computing is now published in Nature! doi.org/10.1038/s415... Congratulations to all the authors on this exciting achievement! 🧬 An accompanying Research Briefing is also available here: doi.org/10.1038/d415...

doi.orgA thermodynamically favoured molecular computer - NatureScaffolded DNA Computer performs diverse computations while thermodynamically relaxing towards equilibrium, demonstrating simplicity, reusability, speed, robustness and scalability of the approac...

biorxiv.orghttps://www.biorxiv.org/content/10.64898/2026.09.03.749129v1

9 Sept

New size record in DNA origami nanopores! 🧬

Cees Dekker@ceesdekker.bsky.social

Latest #CDlab paper on BioRxiv: www.biorxiv.org/content/10.6... 1st author Eva Bertosin developed huge DNA origami nanopores that can dilate and constrict in size. With diameters up to 87 nm, they can insert into lipid membranes, showing selective transport when filled with nuclear pore proteins.

Erik Poppleton reposted

Clément Canonne

@ccanonne.github.io

8 Sept

Well, this Navier-Stokes affair did blow up in finite time

sltrib.comPlanning smaller homes for Salt Lake City is turning into a big battleWould allowing smaller homes in larger parts of Utah's capital provide a generational shift toward affordability or would it ultimately destroy the character of longtime neighborhoods?

7 Sept

I moved from SLC to the Boston area for uni and was struck by how much of Cambridge/Somerville feels like a better version of SLC’s east bench. Building triplexes with generous setbacks results in density high enough for useful public transit and lively squares that make the city fun to live in.

The Salt Lake Tribune@sltrib.com

Would allowing smaller homes in larger parts of Utah's capital provide a generational shift toward affordability or would it ultimately destroy the character of longtime neighborhoods?

7 Sept

You could live 10 minutes walk from a Red line stop and be on a quiet, tree-lined street with architecture not that different from The Avenues, but also have easy car-free access to the entire Boston metro area. Really hope SLC can figure out urban infill that turns it into a real urban center.

Erik Poppleton reposted

Jill Townley

@jilltownley.bsky.social

27 Aug

How do researchers design an RNA in 3D when no accurate 3D prediction model exists? Eterna's collaboration with the @rdaslab.bsky.social at Stanford was able to design novel pseudoknots using a blend of secondary structure prediction and GenAI design methods. 🧪 #RNAsky

Science Magazine@science.org

On the citizen science platform Eterna, #AI methods matched expert human players at inventing sequences that fold into an RNA pseudoknot, a structure in which loops pair with distant parts of the same molecule. Learn more this week in Science: https://scim.ag/4wOqvuE

Erik Poppleton reposted

Jon Worth

@jonworth.eu

24 Aug

Super animation of trains in 🇫🇷🇩🇪🇳🇱🇧🇪🇱🇺🇨🇭 chillchamp1.github.io/github.io/#eu A city like Marseille (France's second or third largest, depending how you define it) has so few trains you can barely see where it is

n.prTrump administration wants to allow companies to hack foreign cybercriminalsThe White House memorandum is thin on details, but it aims to give private businesses the ability to sabotage or spy on certain foreign actors.

16 Aug

A letter of marque came from the king To the scummiest vessel I’ve ever seen

NPR@npr.org

The White House memorandum is thin on details, but it aims to give private businesses the ability to sabotage or spy on certain foreign actors.

Erik Poppleton reposted

Jeff VanderMeer

@jeffvandermeer.bsky.social

7 Aug

Pleased to finally announce... Abdication, the last Southern Reach novel! "There will come the days of the watcher, the drowned woman and the shadow of a man who keeps falling apart with each step, but first comes the moment the birds appear at night from the gaps between the stars, far from home."

@lindorfflarsen.bsky.social

25 July

This is an excellent development in the blind testing field! Good luck to the competitors 🧬

Das Lab@rdaslab.bsky.social

RNA flexible? Maybe we can model that. First blind test of RNA 3D *ensemble* prediction — ligand-free SAMURI ribozyme (displayed on a group II intron scaffold) -- #MD and #deeplearning methods welcome, deadline Aug 22, 2026: predictioncenter.org/casp17/targe...

Erik Poppleton reposted

PBF Comics

@pbfcomics.bsky.social

20 July

Erik Poppleton reposted

Kresten Lindorff-Larsen

19 July

It’s time for the World Cup final with one of the greatest footballers that may be playing his last cup So time for a short thread on a link between Messi and an intrinsically disordered protein. 1/n

Erik Poppleton reposted

Carl T. Bergstrom

@carlbergstrom.com

18 July

Emailed two colleagues in the EU tonight and immediately got this in my inbox. We in the states have so much to learn from y'all.