OPunting 2026

On 16th July, fresh after England’s clean defeat to Argentina, OPIG took to the high seas. The OPIGlets pooled our resources and procured punts from many different berths. Organised by Admiral Alexander Hasson, we departed from the Cherwell boathouse and shipped out upriver to the Vicky Arms.

Could you spot the difference?

Bushes were clipped, banks were mounted, and dignity was shed, but progress, in the loosest sense of the word, was made upstream. Two punts eventually reached their destination, where the crews promptly applied the usual restorative. Nobody knew what had become of the others. We decided this was a problem best contemplated over a pint.

The best Boat Race on the Thames

Then, we had our annual Boat Race. Only those who had never punted before could take part. What followed was less a race than a slow-motion dispersal into the surrounding vegetation.

Apparently, Clare won, and Kingsley came last? I wouldn’t know. I can’t remember.

One Year Down: Wisdom from a Former OPIG Newbie

With a new cohort of PhD students arriving imminently and my first year coming to a close, I am about to achieve an important milestone: I will no longer be the newest full-time OPIGlet in the group!

Naturally, this makes me extremely qualified to impart wisdom.

In all seriousness, the first year of a PhD has been a strange and wonderful adjustment. I have learned a lot about nanobodies, of course, but I have also learned quite a bit about how to actually do a PhD. So, for the incoming OPIGlets—or anyone else embarking on their first year—here are a few things I wish I had fully appreciated when I started.

Give some structure to all that freedom

One of the strangest things about starting a PhD is suddenly having an almost completely self-guided schedule. It is not something most of us have had to deal with before. Undergrad comes with lectures, tutorials, deadlines, and exams. Most jobs come with meetings, working hours, and someone telling you what needs to be done.

Then you start a PhD and are essentially handed a very big question and an expanse of time that somehow feels both enormous and nowhere near long enough.

I found that giving myself a schedule helped enormously. For me, that means coming into the office at around 9:30, working properly while I am there, and heading home at around 5:30. The beauty of a self-guided schedule, though, is that it can be whatever works for you. If you are a night owl and your productive hours are 2 pm to 10 pm, embrace it. The important thing is having enough structure that “I can work whenever I want” does not quietly turn into either “I am always working” or “I have somehow done nothing today.”

Regular meetings with your supervisor are invaluable for the same reason. OPIG supervisors are great about this, and I have come to really value my one-to-ones. Having someone look at your work with fresh eyes, hold you accountable, and help turn a huge research question into tangible goals can be a complete lifesaver. When you have spent several days staring at the same problem, it is remarkably easy to lose all sense of what is obvious, what is important, and what you should actually do next.

Remember that a PhD is a marathon

This is probably the lesson I am still learning.

A PhD is long. You do not need to solve everything this week. Take breaks. Go home. Do things that have absolutely nothing to do with your research. Often, stepping away from a problem and coming back with a clear head will get you further than another three hours spent stubbornly staring at it.

I did not take enough proper breaks this year, and it caught up with me a bit. After a very healthy three-week stint back home in Canada, however, I am rearing to go for another year of nanobodies.

Ask me again how I feel about them next summer.

Get involved in the group

At the beginning of each year, Charlotte assigns everyone in OPIG a group job, so you will, to some extent, be forced to get involved. My advice is to embrace it.

This year, I was one of the OPIG social secretaries and co-organised the OPIG retreat. Organising the retreat was, at times, unbelievably stressful. It was also incredibly rewarding to see everything come together and watch the whole group enjoy such a great week.

More generally, getting involved has made me appreciate how much the people around you shape the PhD experience. Research can be frustrating and occasionally quite isolating, so having a group of people you actually enjoy spending time with makes an enormous difference. Fortunately, OPIG is full of very cool people.

Let your colours show

Finally, do not feel like you need to become a Very Serious Academic™ the moment you start a PhD (or ever, if you are Professor Charlotte M. Deane MBE FRS).

This year, I decorated the office for essentially every holiday or season I could justify and persistently pestered anyone who would listen into coming rock climbing with me. The decorations have received enough appreciative comments that I intend to continue inflicting them on the office, and I have managed to establish something of an OPIG climbing cult, if I do say so myself.

These things might have very little to do with my actual research, but they have been some of my favourite parts of the year. A PhD takes up a significant chunk of your life, and the people in your group are the people you will spend a lot of that time with. Bring your interests with you. Organise events. Be enthusiastic about things. Make the place somewhere you actually enjoy being.

And, obviously, when you join OPIG, you should come bouldering.

One year down

I am certainly not claiming to have figured out how to do a PhD after one year. If anything, I think I have become increasingly aware of how much I haven’t figured out.

But I have learned that a little structure goes a long way, that taking time away from research is part of doing good research, and that there is much more to enjoying a PhD than the work itself.

So, to the new OPIGlets: welcome! Make a schedule. Take breaks. Get involved. Bring whatever weird hobbies and interests you have with you.

And good luck avoiding the climbing cult.

Is the race for AGI a scam? Are the tech bros con men or visionaries?

To find out, we formally introduce the Stinkometer

In research, it can be tough even for experts to tell fact from fiction. This is especially true for more speculative fields like AI. It can feel like every model is “State-of-the-Art” and that AGI (whatever that means) will be “6 months away” for at least the next 6 months. How do we know we can trust these people?

What is a visionary? What is a con man?

Visionaries sell a fringe idea of the future, usually with strong self-belief and charisma. Con men are visionaries who don’t believe what they’re saying. It’s hard to tell the difference because we can’t read minds and can’t see the future.

I solved this by adapting the insightful “New Political Compass” from Harper O’Connor, an American political YouTuber. Harper found a similar problem. He’s active in local politics and has to decide who he should build alliances with to tackle certain issues. Interestingly, the “left-right” axis wasn’t a helpful guide. Most people he canvassed were reasonable but didn’t follow politics closely enough to have a robust ideology. He realised that someone’s psychology can be more important than their stated ideology.

Therefore, it was more useful to ask: Am I talking to a reasonable person? Here, I expand his framework into the Belief Compass (or the “Stinkometer”). We can answer our question by answering three simpler ones:

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Predicting ADME Properties with Machine Learning: 82% of the Performance From Two Descriptors

A Nature survey of ~1500 scientists reported that more than 70% had failed to reproduce another scientist’s experiments, and 50% had failed to replicate their own (Baker, 2016). This study wasn’t specific to machine learning, but the crisis has its own flavour in computational drug discovery.

One aspect of this is that available datasets have known quality issues, and results built on them can be fragile. MoleculeNet and the Therapeutic Data Commons (TDC) opened drug discovery to a wider ML community, but they’re no longer sufficient for driving further advances (Wognum et al., 2024).

Amongst a number of issues, 71% of molecules in one MoleculeNet dataset (BACE) contained at least one undefined stereocenter (a point where the same atoms can sit in two different 3D arrangements), making it unclear what chemical entity is actually being modelled (Li et al., 2026).

The stakes are high. In 2017, a research group found their cancer-target inhibitor inactive from one vendor and highly active from another. Eventually they traced this to vendors selling different mixtures of the compound’s two 3D forms where only one was active on the target and mechanism they were investigating (Baker, 2017).

Most approved pharmaceuticals are relatively small chemical molecules, typically weighing under 900 g/mol, with most of the rest being biologics. Whilst in Oxford on the UNIQ+ summer internship programme, I focused on ADME, an aspect of early stage drug discovery, where assays are measured in vitro as a stand-in to predict how a compound will behave in vivo (in the human body) before clinical trials. Absorption (does it enter the body), Distribution (where does it go), Metabolism (how quickly it’s transformed) and Excretion (how quickly it’s eliminated) are processes critical to whether a candidate succeeds. 

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Project Cybersyn: Bayesian Socialist Algocracy in 1970s Chile

Palantir and Peter Thiel have found themselves in the headlines a lot this year, very often in the same sentence as the word “surveillance”. The idea behind Palantir is a simple one: give one company, or one control room, a real-time algorithmic view of how a government or an economy is actually functioning, and let them help run things better.

That idea is not new. In 1971, Salvador Allende’s socialist government in Chile built almost exactly that system, out of telex machines and a room full of fibreglass chairs, on practically no budget. There’s evidence it worked, until a coup destroyed it before anyone found out whether it would have worked at scale. This was known as “Project Cybersyn”.

A modern reconstruction of Project Cybersyn’s hexagonal operations room, with seven chairs arranged in a ring and display screens on the walls.
The space-age themed Opsroom, where decisions were made in response to Bayesian forecasting.
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The cost of a better pose: balancing GNINA sampling and runtime

If you have ever set up a docking experiment or tuned a docking workflow for GNINA, you may have found yourself asking:

What are the “best” settings for running GNINA?

Unfortunately, there is no single objectively correct answer. The optimal settings will depend on the input data, the goal of the docking experiment, and the computational resources available. One reasonable approach is simply to use the standard GNINA settings, dock each molecule once using a single conformer, and leave it at that. The default settings already perform well in many cases. But that does not mean performance cannot be improved!

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Beyond the Vaccine: AI’s Expanding Role in LNP mediated Drug Delivery

Lipid nanoparticles (LNPs) have evolved from a specialised drug-delivery technology into a cornerstone of modern medicine. Their success became evident during the COVID-19 pandemic, enabling the delivery of the mRNA used in the Pfizer-BioNTech and Moderna vaccines. However, their applications extend far beyond vaccination, as LNPs can also deliver siRNA, plasmid DNA and gene-editing machinery, creating opportunities to treat genetic diseases, cancer and many other conditions.

Yet a fundamental challenge remains: how do we design an LNP that delivers the right payload, to the right cells, in the right place?

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Claude now watermarks its text: here’s what is actually happening under the hood

On 11 August Anthropic announced that every Claude model released after 2 August 2026 will watermark the text it produces. Not just in the chat app: the watermark lives at the model level, so it is there whether the text came through the API, Claude Code, Cowork, or anything else built on top. A follow-up post a few days later explained the mechanism, and the short version is that it’s a version of DeepMind’s SynthID-Text, which in turn descends from a scheme Scott Aaronson sketched out while at OpenAI in 2022.

Predictably it has caused a lot of confusion, especially in the academic circles (“is it zero-width characters?”, “can I strip it with a regex?”, “does this mean Turnitin finally works?”), most of which comes from not knowing how an LLM actually turns a probability distribution into words. So this post starts there, builds the watermark up from the sampler, and then tries to be honest about what it does and doesn’t mean for people who write papers and mark essays for a living.

Nothing here is hidden: the watermark is not metadata, not invisible Unicode, not a hidden token. It is a statistical pattern in which words were chosen, which is exactly why it survives copy-paste and exactly why it fades when you rewrite.

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Diffusion Models Can’t Give You a Likelihood… So How Do We Score Inverse-Folded Sequences?

I’ve been working with inverse folding models for sequence design for a while now, and one question kept coming up. How would you score a sequence’s likelihood under these models? It turns out the answer depends heavily on whether the model is autoregressive or diffusion-based.

Autoregressive models, like GPT-style language models, make this straightforward. You can calculate the probability of a sequence directly, by breaking it into one prediction per position and multiplying them together. Diffusion models define a probability distribution over outputs too, but getting the likelihood of a particular output means accounting for many unobserved intermediate states, and that turns out to be much harder. This is why diffusion models typically rely on the Evidence Lower Bound, or ELBO, a computable estimate, rather than the exact likelihood itself.

The easy case: autoregressive models

An autoregressive model breaks the probability of a sequence into a product of conditional probabilities:

p(x1:n)=∏i=1np(xi|x<i)p(x_{1:n}) = \prod_{i=1}^{n} p(x_i \mid x_{<i})
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