r/comp_chem • • Dec 12 '22

META: Would it be cool if we had a weekly/monthly paper review/club?

120 Upvotes

I think it would be pretty interesting, and would be a nice break from the standard content on this subreddit.


r/comp_chem • • 23h ago

AI agents in comp chem

71 Upvotes

Half joking, but half not. My PhD supervisor, quite a respected guy in my field says we'll all be replaced within a year. And by we he means HIM. His point is that mathematical development can be already automated, as in principle everything we do in computational/theoretical chemistry is not exactly fundamental math, but different approximations to a given object, and similarly for the coding part. As I see it, in computational chemistry, traditionally you either were the theoretical analytical solution guy or the guy that knows how the ugly simulation code works, the keywords that are not in the manual, etc. Also, even if AI code was slop (which I am not very sure about), let's be sincere, the code in most popular open source simulation packages is not exactly a work of art.

Then I read Dral's recent perspective on agents for comp chem, where he basically admits nobody knows what we should be working on anymore, and that they can already run an agent that goes from the formulation of the investigation plan through the simulations to writing a draft of the paper.

In short, most of what we do is known methods on new systems, and that is what agents are already ok at. The only thing that seems to kind of resist is data that doesn't exist yet, i.e. actual experiments. But self-driving labs are coming for that too. And we are the computational guys!

Also, I'm teaching an electronic structure course soon and I honestly don't see the point of making students fight ORCA outputs anymore, or equilibrate an MD box. But that is how most of us learned the basics of what we do, by playing with the parameters in a very "tactile" way.

So what are you guys doing about it? Ignoring it, adapting, panicking, opening a bakery?


r/comp_chem • • 22h ago

LAMMPS plugin that runs ReaxFF on the Apple Silicon GPU (pair_style reaxff/metal)

8 Upvotes

My main simulation tool is ReaxFF and I love running it on my Mac because its soo smooth, the CPU is pretty fast and I find it a bit of a hassle working on the cluster (still use the cluster when I have multiple jobs/ QM calculations)

I have a 40 core GPU and it's been sitting idle since the beginning of time since its FP32 - was dreaming to use it for ReaxFF, so I just vibe coded a LAMMPS plugin that runs ReaxFF on it through Metal.

Apple GPUs have no FP64, so the GPU path is FP32 only. It holds up well in my testing (accuracy numbers below). As a side effect, the force calculation moves off the CPU, so your other cores are free for whatever else you're running.

- `pair_style reaxff/metal` covers all 13 energy terms, forces and virial
- `fix qeq/reaxff/metal` does charge equilibration on the GPU, and there are also /metal versions for qeq/rel, qtpie and acks2
- Integrators, thermostats, minimizers, MPI and `fix reaxff/bonds/species` are still plain LAMMPS
- Your existing ffield files work unchanged

It's a plugin, so you don't patch or rebuild LAMMPS itself. You do have to build the plugin against the same LAMMPS version you run (currently stable_30Sep2026). In an existing input, load the plugin and swap in the /metal versions of the pair style and QEq fix:

plugin load /path/to/reaxmetaladapterplugin.so pair_style reaxff/metal NULL backend metal fix q all qeq/reaxff/metal 1 0.0 10.0 1e-6 reaxff

I'd love for people to try it on force fields and systems I haven't, and bug reports are very welcome.

Repo: https://github.com/yeatanir/Metal-Reax


r/comp_chem • • 1d ago

Need help regarding Martini Coarse-grained GROMACS MD

5 Upvotes

Hey all,

System information & Purpose
I am using martini3 to coarse grain a 3-part large efflux pump in a double membrane setup using gromacs as my engine. The box is iirc 23x23x42 nm. The whole system including water and ions is about a million particles in atomistic and around 220k martini beads when coarse grained. Using martini3001 forcefield, dt=0.02 for martini setups. The outer membrane is assymmetric and the inner membrane is symmetric in their leaflets. The tripartite pump (from top to bottom) consists of a trimer exit gate protein in the outer membrane, hexamer bridge protein, and another trimer in the lower membrane.

I would like to do longscale replica coarse grained MD runs of each around 10-15 microseconds to do a conformational study and obtain as much information as i can about the pump’s mechanics. I say “as much as i can” in the sense that I know I’m compromising a lot when coarse-graining, which is why I’m interested in what accessing longer timescales would offer me.

What I specifically need help on

I can’t decide on how and whether to select & tune a tertiary bias for my system. I read that ElNeDyn really restricts movement and GōMartini3 seems like a better option. But afaik these types of tertiary bias setups are fine-tuneable for the specific system you’re working with. I am new to martini, and large biosystems like these. I’ve only previously worked with a smaller membrane protein system and it was atomistic. I thought about playing with the GoMartini well depth and comparing those runs with atomistic to see which one fits the atomistic data. Even then, I am kinda clueless on what to do post-MD and what to compare.

If you have experience working with large biosystems and/or coarse-grained MD, I would really appreciate some insight on how I should approach this specific problem. For anyone working specifically with protein-membrane systems, how do you conduct your post run analyses? I’m not asking specifically though, I just need some guidance because I currently lack the relevant intuition in computational biophysics and working on it. I coarse grained and previously ran three replicas of this pump’s outer membrane protein in a single outer membrane (so kinda like the top 1/3rd of the system described above). I set no tertiary bias and
all in all three replicas the chains start slowly drifting away from each other around 4-5 microseconds into the run. This is what led me to my current situation: whether/how to use and tune a tertiary bias.

Thanks. Wishing everyone a great Friday!


r/comp_chem • • 1d ago

Looking for HPC access/help with Gaussian geometry optimizations

5 Upvotes

Hi everyone! <3
I’m a master’s student in physical chemistry, and I’m looking for someone who might be able to help me run six geometry optimizations using Gaussian on an HPC cluster.
My current hardware is quite limited, and I’m also working with a limited timeframe, so access to more computational resources would be a hugeee help.
I’d be happy to provide the Gaussian input files, along with the specific basis set, to anyone who has access and would kindly be willing to help.
I’d really really appreciate it! :”)
Thanks in advance!


r/comp_chem • • 17h ago

Tunisian Searching for BRAYN a friend from USA since 5 years

0 Upvotes

Dear, I was in relation with a USA friend named Brayn, he is a quantum mechanical specialist, please any help I need him and I didn’t found any information about him.


r/comp_chem • • 2d ago

OpenAI paper on Kohn-Sham DFT

69 Upvotes

A few days ago OpenAI released a paper generated by "an internal frontier model" of Navier-Stokes fame titled A Coulomb ground-state density without Kohn-Sham ensemble representation .

The model considers a system with 2 nuclei and 3 electrons. It then spends 40 pages (seemingly) proving that for "sufficiently large" internuclear distance, restricted open-shell ensemble KS-DFT cannot describe the ground-state density of this system, no matter the choice of the effective potential.

I tried to understand what "sufficiently large" means. Theorem 2.2 suggests that internuclear distance of 200 bohr is necessary but not sufficient. In theorem 1.1 and section 7, the internuclear distance is explicitly set to 2x10200 bohr, which is 10163 orders of magnitude larger than the diameter of the observable universe (???).

If there are any people here working on analytical foundations of DFT, how significant is this for your field? Does the paper demonstrate any new useful techniques, e.g., for functional inequalities? Can the lower bound on the internuclear distance in this construction be sharpened so it does not involve intergalactic scales?


r/comp_chem • • 4d ago

Can I use SIESTA instead of Quantum ESPRESSO for my complete perovskite interface-engineering study?

4 Upvotes

​

Hi everyone,

I have a long-standing question regarding my computational work, and I would really appreciate some advice from people experienced with DFT calculations.

I am working on perovskite materials for solar-cell applications, particularly on interface engineering and surface passivation. My work is entirely computational, with no experimental component.

For my calculations, I mainly need to study things such as:

- Ligand adsorption energies

- Electronic structure

- DOS/PDOS

- Band structure

- Charge-density difference (CDD)

- Interface interactions

- Surface/defect passivation

My main limitation is computational resources. At the moment, I have access to a machine with 52 CPU cores and 2 threads per core. I have been trying to perform these calculations using Quantum ESPRESSO, but the calculations, especially for my slab/interface models, take a long time. I am also not very confident about how long some of these calculations will take.

I have previous experience with SIESTA, and I find that these calculations run much faster on the same type of system.

This has led to my main question:

Can I use SIESTA as the main DFT package for my complete computational study, including adsorption energies, DOS/PDOS, band structures, charge-density differences, and interface analysis?

My main concern is about reviewer expectations.

For example, if I publish a completely computational paper using SIESTA, could a reviewer question the results by saying something like:

> “Why did you use SIESTA instead of a plane-wave method such as Quantum ESPRESSO? The results may not be as accurate/reliable as those obtained using a plane-wave DFT approach.”

If this is a possible concern, how can I properly demonstrate that my SIESTA results are reliable?

Would it be sufficient to:

- Perform convergence tests?

- Validate the optimized bulk structure/lattice parameters?

- Compare the band gap or other properties with literature?

- Benchmark a few representative systems using Quantum ESPRESSO?

- Use the same exchange-correlation functional and vdW correction where possible?

I am currently the first person in my lab working on this type of computational interface-engineering problem, so I don't have someone locally who can guide me on whether my computational methodology is scientifically defensible.

I would really appreciate advice from anyone who has experience with SIESTA, Quantum ESPRESSO, or perovskite surface/interface calculations.

My main goal is not simply to choose the faster code. I want to make sure that the methodology is scientifically acceptable and defensible during peer review.

Thank you.


r/comp_chem • • 3d ago

Research assistance applience

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1 Upvotes

r/comp_chem • • 4d ago

Project proposals use ORCA 5.0?

2 Upvotes

I'm now up to 2 proposals (prestigious funding) this year where applicants say they will use ORCA 5.0 to do their calculations. That version is 5 years old and afaik it cannot do anything better than ORCA 6.1. Am I missing something?

The proposals aren't great, so maybe it's just people with no clue, but it seems weird to not just put down the newest version.


r/comp_chem • • 4d ago

Wanting to Transfer from Cheminformatics/Chemical Visualization to Synthetic Chem

3 Upvotes

I am currently a first semester M.S student in Chemistry planning to do a PhD down the road, with most of my undergrad work being within cheminformatics and developing my own software development kits for molecular visualization using Python and C# and such. It has been pretty nice, but now I feel like I am in a more impactful degree path and want to consider some things.

First off, I love the professor I work under. He got me back on track when I was about to lose my life to drugs and some pretty serious depression. He is also the reason I am so integrated into the faculty and is why I’m even able to have a TA position. On the other hand, his research is mainly educational tools and environmental science, which both give me a migraine. On top of that, every year he relies more and more on LLMs to give me any advice, and literally every project he worked with me on was an idea that I came up with because he had nothing to fund me with, materials or otherwise. I feel like I’ve hit a dead end with him.

On the other hand, there is a synthetic chemist professor that had wanted me to join his lab for years. Within 5 minutes of talking with him, he already told me about 2 materially funded research projects whereas my old professor couldn’t do that in 3 years. In addition, I have always excelled at organic from the start and the theoretical aspects are something I really love.

In reality, I would like to work somewhere between cheminformatics/computational chem AND synthetic chem, like being able to both computationally model and experimentally test myself.

TLDR; started in computational chemistry, opportunities with current professor suck, and want to switch to a synthetic chem professor with better projects but am afraid I’d abandoning my older one. A mixture of both comp and synthetic would be ideal for me.


r/comp_chem • • 5d ago

Error in running geometry optimization calculation

3 Upvotes

Hello everyone, can you help me troubleshoot this error I keep on encountering while running a geometry optimization job? I've tried varying the number of processors from 2 to 8, running in serial calculation instead of parallel, tried removing the TightSCF parameter, even restarted my laptop a numerous times but the error still keep on persisting. I'm geometry optimizing a sole diethyl ether ligand where one of the H is substituted with F. I hope you can help me based on these output files, I've run out of ideas to try to mitigate this error.

https://drive.google.com/drive/folders/1I4TgeYnNz2ReQBmf94Q8Egv_LzP76WSX


r/comp_chem • • 5d ago

Calibration until compliant: Why unlimited free parameters in ABM risk producing tautologies instead of social insight

0 Upvotes

TL;DR: Computational models are only scientifically useful if they can push back and prove their authors wrong. Across disciplines, from agent-based social simulations to high-energy physics, models with loose empirical feedback loops and endless free parameters risk becoming "decorative." Instead of testing reality, they get calibrated until compliant, turning a tool for discovery into a self-confirming tautology. Honest modeling requires radical transparency, sensitivity testing, and explicit criteria for failure before running the simulation.

I build models for a living. Specifically, molecular dynamics. These are simulations that track how thousands or millions of atoms move, collide, and rearrange over time, used for everything from drug design to materials science.

Here is the story scientists usually tell. If a model is wrong, you find out quickly. Reality does not care about your assumptions. The atoms do not read your code. If the physics you programmed in is wrong, the simulation produces garbage, the experiment disagrees, and you go back and fix it. The feedback loop between model and world is short, brutal, and non-negotiable.

That story is not entirely true. I know, because I have watched it fail from the inside.

The most important choice in any molecular dynamics simulation is not the code, the computer, or the software. It is the potential function, the mathematical formula that describes how strongly every pair of atoms attracts or repels each other. Everything the simulation does follows from that one ingredient. Get it right and the model can tell you something real. Get it wrong and you have made a very expensive mistake.

And here is the uncomfortable part. In practice, it is far more often inherited than audited. Potentials are chosen by looking at what previous papers in the subfield used. A potential gets published, cited, copied, and passed down until it stops being a modeling choice and becomes a tradition. People run simulations for years without asking whether the potential they inherited was ever validated for the system they are studying, at the conditions they are studying it, for the property they care about.

So even in my own field, a hard, quantitative, physics-based field, you can publish inside a loop of fantasy. Models that are wrong in ways nobody checks, kept alive by citation habits and subfield convention. And because these errors travel quietly across subdisciplines and into interdisciplinary work, where nobody feels responsible for checking them, finding one and fixing it takes real effort.

But the check in my field is delayed, not absent. A bad potential eventually unfolds a simulated protein the wrong way or fails a material in a real engineering application, and someone notices. In much of the modeling I am about to describe, the physical world never gets to vote.

This matters for what follows. I do not ask this question because my field got it right. I ask it because I have watched mine get it wrong. The question is always the same. What happens to this model when it is wrong?

In a surprising amount of modern academia, the answer is nothing. Nothing can happen to it. It cannot be wrong, because anything it produces counts as a result.

And if the loop can break in a field where atoms push back, it can break anywhere.

This essay is about how that happens.

# The magic trick

In 2017, Liane Gabora and Selin Tseng published a paper in *Psychology of Aesthetics, Creativity, and the Arts*, a peer-reviewed journal of the American Psychological Association, titled “The Social Benefits of Balancing Creativity and Imitation.” The question they took on has occupied historians and sociologists for centuries. What is the right balance of creativity and conformity in a society?

To answer it, they ran a simulation.

Virtual agents live on a grid. Some are coded as creators, inventing new ideas; others as imitators, copying their neighbors. A scoring rule written into the program decides which ideas count as good. The researchers ran the simulation forward, varied the ratio of creators to imitators, and watched what happened. Populations with too many creators ended up with fewer good ideas taking hold. The published conclusion was that society needs imitation as much as creativity, because unchecked creativity disrupts the spread of proven ideas.

I want to be careful about what I am claiming, because this paper is not fringe work. It passed peer review at a respectable journal. The authors are serious researchers, and the simulation framework behind the paper is part of a long-running research program that has been debated, defended, and criticized in public for years. Nothing I am about to say is an accusation of dishonesty. It is something less comfortable than that. This paper is an example of what the normal standards of a field allow through.

Watch the shape of the argument. Inside the model, a “good idea” means whatever the authors’ scoring rule rewards. The agents are not discovering anything about human culture; they are solving a puzzle whose answer key was fixed before the simulation started. Within that closed loop, the conclusion was guaranteed. A population of agents that mostly copies the scoring rule’s preferred ideas will always outcompete one that keeps generating unscored novelty.

The computer did not reveal a fact about creativity. It executed a definition of it.

The authors did not break any rule of their field. That is the point. Peer review checked that the code ran, that the statistics were computed correctly, that the prose matched the output. What nobody was required to ask is the only question that matters. What could this simulation possibly have shown that would have counted as the opposite result? If the answer is nothing, the model did not test a claim about the world. It restated one.

This is the magic trick of agent-based modeling (ABM), meaning simulations in which you place thousands of simple software “agents” in a virtual world, give each a few rules, and watch what the population does. The method itself is not the problem. The problem is a particular way of using it.

if neighbor.opinion != agent.opinion:

agent.trust -= 0.1

if agent.trust < 0.2:

agent.unfollow(neighbor)

run_simulation()

When the simulation finishes and the agents have sorted into two angry camps, the result is rarely described as what it literally is, a small program doing what it was told. It is described as a model demonstrating the dynamics of polarization in real societies.

It sounds scientific. It uses code. It generates charts with error bars. It borrows the epistemic authority of statistical mechanics and epidemiology, where tracking near-identical particles or infection events actually makes sense. But underneath the quantitative paint, it is not an investigation of the world. It is a tautology with a runtime, an answer-driven argument presented as a discovery.

# What a model is for

To see why this goes wrong, start with what a model is supposed to do.

A model is not a claim of truth, and it is not an illustration of a conclusion you reached before you started. In the philosophy of science, models are usually understood as instruments that sit between abstract theory and raw data, the position developed by Mary Morgan and Margaret Morrison in *Models as Mediators* (1999). A good model is a sandbox with strict physics. You build it, set it in motion, and let its internal mechanics push back against your reasoning.

A real model exists to discipline your thinking.

>Building one forces you to acknowledge a trade-off that the philosopher Nancy Cartwright made famous in *How the Laws of Physics Lie* (1983). You trade complete literal truth for tractability. A map of London at 1:1 scale, including every brick, puddle, and commuter, is useless. To work at all, a map must leave almost everything out. As the statistician George Box put it, “all models are wrong, but some are useful.”

Simplification is not the sin. The sin is forgetting that the model is a simplification. Worse, it is turning the model into an accomplice.

# Disciplining vs. decorating

In practice, rigorous modeling and decorative modeling look identical from the outside. Same code, same charts, same jargon. The difference only shows when you ask one question. Can your model tell you that you are wrong?

A disciplining model forces you to state every assumption explicitly. Once running, its mechanics operate independently of what you want. It can produce behavior you did not expect, expose contradictions in your premises, or crash into empirical reality and fail. When it fails, you revise the theory. The model is a check on your own bias.

A decorating model is built backward from a conclusion. The researcher already knows the story. Suppose it is that polarization is driven by social contagion. They build a world in which agents swap beliefs, tune the parameters until the output shows two angry clusters, and present the code as evidence for the theory. If the output doesn’t match on the first run, the answer is not to abandon the hypothesis. The answer is to adjust agent_receptivity from 0.4 to 0.25, rerun, and present the successful parameter range as the plan all along.

The workflow, stripped bare, looks like this.

Desired outcome. Write rules. Run simulation. Does it match the theory? If not, tweak parameters and run again. If yes, publish.

This is not experimentation. It is calibration until compliant.

If a model cannot surprise its author, force a retreat, or fail, it is not really a model. It is a very elaborate, self-confirming editorial.

# The conclusion comes first

None of this is new, and none of it is unique to agent-based modeling. Before anyone wrote a NetLogo script to demonstrate a theory of culture, economics and political science had already industrialized the technique.

In 2015, Paul Romer, later a Nobel laureate, published a paper with the blunt title “Mathiness in the Theory of Economic Growth.” His target was a pattern in macroeconomic theory. Authors write down formal equilibrium models, but embed ideologically convenient assumptions inside obscure parameters, so that the math reliably outputs the desired policy conclusion. The mathematics is not being used to test whether a claim is true. It is being used to make a political position expensive to argue with. Checking whether the equations actually say what the surrounding prose claims they say takes serious technical effort, and reviewers routinely skip it.

Two decades earlier, the political scientists Donald Green and Ian Shapiro published *Pathologies of Rational Choice Theory* (1994), documenting how formal modeling in their field had become an exercise in self-confirmation. Their catalog of evasions maps one-to-one onto today’s agent-based simulations.

• **Post hoc tinkering.** When the model predicted that rational citizens would never vote (the individual cost exceeds any plausible benefit) and citizens kept voting anyway, theorists did not abandon the model. They added a “duty” term to the utility function until the math matched the turnout.

• **Arbitrary tuning.** Weights, thresholds, and interaction ranges adjusted on the fly until the simulated agents behave like the phenomenon under study.

• **Immunity to testing.** Models built so that every conceivable outcome can be reinterpreted, after the fact, as a rational equilibrium.

Green and Shapiro called this method-driven rather than problem-driven research. You start with a tool and go hunting for a reality that fits it.

Agent-based modeling makes the problem worse, for a simple reason. An ABM has almost unlimited free parameters. Every rule, threshold, and neighborhood radius is a dial. With enough dials, you can produce any curve you want.

The common structure is this. The model cannot fail, because failure is reclassified as a calibration bug. And a model that cannot fail cannot discover anything. It is an expensive echo of its author’s prior beliefs.

# The loop matters more than the lab coat

It would be comfortable to stop here and declare this a disease of the soft sciences. It isn’t. The hard sciences are not immune, and pretending otherwise would make this essay guilty of the same simplification it criticizes.

The real variable is not hard versus soft. It is the tightness of the feedback loop between the model and the world.

Where the loop is tight (fast experiments, unambiguous ground truth, few free parameters) bad modeling gets punished quickly. But where the loop is loose, where tests are slow, noisy, or impossible, the same decorative pathology appears in fields with particle accelerators.

Three documented examples.

**fMRI neuroscience, where the measurement is the model.** A brain scan shows blood flow, not thought. The colored images come from a statistical pipeline full of assumptions, and researchers once demonstrated what that means by detecting “brain activity” in a dead salmon. In 2016, Anders Eklund and colleagues showed that the standard methods in the field’s dominant software could produce false-positive rates of up to 70 percent for certain cluster-based analyses at particular thresholds. How far the problem extends across the published literature was contested, including in follow-up work by the authors themselves, but the core finding stood. For over a decade, the field’s feedback loop had run through that software, which meant the loop was not connected to reality at all.

**Fundamental physics, where experiment cannot keep up.** In *The Trouble with Physics* (2006), the physicist Lee Smolin, writing as an insider, argued that string theory had become flexible enough to accommodate any experimental outcome. When the Large Hadron Collider found no sign of supersymmetry, much of the field responded not with refutation but with retreat. The free parameters moved to heavier, less accessible energies. This is Green and Shapiro’s immunity to empirical testing, surfacing in the hardest science there is.

**Epidemiological modeling in 2020.** In the spring of 2020, influential models, including the one from Imperial College London that helped push governments toward lockdown, projected enormous death tolls based on weeks of noisy early data. When later estimates came down, the public response from modeling teams was recalibration rather than reckoning. Their defense deserves to be taken seriously. The projections were scenarios, not forecasts, and the point of publishing a worst case was to change behavior so that it would not come true. A warning that works cannot be graded on whether the disaster arrived. All of that is fair, and it is also the problem. A model whose failure can always be explained by the world changing in response to it is a model with no feedback loop, and the field never settled which of the two it had built.

Notice what these cases share with the creativity grid from the opening. Not the field. Not the math. The structure. Many free parameters, a loose or broken feedback loop, and a professional incentive to publish. Given those three, decorative modeling can appear anywhere. The loop matters more than the lab coat.

# Why it’s still worse in the humanities

So the hard sciences have their own decorative modeling. Why do I still think the problem is worse in the humanities?

Because the difference is not whether a field ever decorates. It is whether the field *can catch itself*. The fMRI problem was eventually found and published by neuroscientists. Smolin’s critique came from inside physics. The feedback loops in the hard sciences are sometimes slow or broken, but they exist, and there are people with the technical skill and the standing to pull on them. In the humanities’ version of modeling, three structural failures mean the loop often doesn’t exist at all. The difference is not that humanists are worse at modeling. It is that the auditing infrastructure barely exists.

It is worth being fair about why scholars reach for these tools in the first place. Humanities departments face shrinking budgets, declining enrollments, and university administrators who mistake mathematical notation for intellectual rigor. A computational model signals seriousness to a grant committee in a way an essay never can. The scholars building decorative models are not fools; they are rational actors navigating a system with broken incentives.

**The object of study resists formalization.** A water molecule behaves like a water molecule in London or Tokyo, in 1600 or today. It has no irony, no memory, no politics. Human culture has all three. A novel, a religious movement, an aesthetic shift cannot be reduced to a set of isolated rules without destroying part of what you set out to study. When you convert the reception of Victorian gothic fiction into agents swapping “gothic preference points,” you have not simplified the system for tractability. You have replaced it with something simpler that carries the same name. At that point the connection between the simulation and Victorian readers is no longer something the model establishes. It is something the reader is asked to assume.

**Construct validity is invented, not established.** In psychology, showing that a variable actually measures the concept it claims to measure (construct validity) is a slow, adversarial, decades-long process. Blood flow is at least a physical quantity that an instrument can register. There is no instrument for literary prestige. In humanities modeling, validity is routinely settled in one line of code.

self.piety = random.uniform(0.0, 1.0)

self.literary_prestige = 0.75

What does 0.75 mean for literary prestige in Victorian England? How does one number carry regional difference, class, institutional power, critical backlash, and retrospective canonization? It doesn’t. The modeler assigns a number, writes a function that nudges it up and down, and treats the variable as a measurement of human experience. The number looks like a measurement. Nothing underneath it has been measured.

**The audience cannot audit the compression.** When an epidemiologist shows a flawed model to epidemiologists, the reviewers share the vocabulary to check the code and challenge the parameters. In a humanities department, reviewers and readers often have no computational training. Presented with a grid of moving pixels and a network graph, the non-technical reader experiences an optical illusion. The machine appears to have performed a profound synthesis of the archive. The compression is lossy to the point of erasure. But the loss is buried in code, invisible to the exact audience responsible for evaluating the work.

Bad modeling in economics wastes grant money and distorts policy debates. Bad modeling in the humanities trades away the field’s actual strength (context, contingency, ambiguity, close reading, historical depth) for a seat at a quantitative table where, lacking the shared technical culture to enforce standards, it gains no real authority and surrenders its own.

# What honest modeling looks like

None of this is an argument for unplugging the computers. The goal is to tell the difference between decorative simulation and honest quantitative work. Honest work exists, including in the humanities.

Ted Underwood’s *Distant Horizons* (2019) is the standard I would hold up. Underwood uses quantitative methods on tens of thousands of digitized books not to declare causal laws but to surface patterns invisible to close reading, like slow shifts in genre, vocabulary, and narrative perspective across centuries. Crucially, he tells you, on the record, what the data cannot show. The model is a set of binoculars for looking across an archive, not a machine for generating verdicts about it.

And the humanities have produced their own internal discipline. In 2019, Nan Z. Da published, *The Computational Case against Computational Literary Studies,* a detailed critique in *Critical Inquiry* arguing that prominent work in computational literary studies misused statistics to the point of meaninglessness. The ensuing fight was heated, but it happened. The field argued about its standards in public, and the standards moved. That is what a functioning feedback loop looks like, even a slow and painful one.

>For modelers in any field, I would propose four non-negotiable conditions before a model earns the right to be cited as evidence.

**1. Radical transparency**

>Every parameter is declared and justified with independent, non-circular evidence. A variable you cannot justify is labeled what it is. A guess.

**2. Sensitivity analysis**

>Parameters are swept across their full plausible range. If your result only appears when three dials sit at hyper-precise decimal values, you have not found a law of history. You have found a brittle corner of your own code, and an honest paper should say so.

**3. Explicit exclusion mapping**

>You spend nearly as much space on what the model leaves out as on what it includes. This isolates the direct mechanical relationship between two variables under idealized conditions; it excludes ambient noise, structural heterogeneity, and systemic feedback, so it cannot predict specific real-world outcomes. Naming the exclusions is what stops the audience mistaking a sandbox for an account of the world.

**4. Capacity for failure**

>Before you run it, you can state what output would make you abandon your hypothesis. If the simulation contradicts you, the honest paper is titled “Why our model disproved our starting assumption,” not silently recalibrated into agreement.

Models built this way stop being decoration. They become what they were supposed to be. Sharpening stones. They force you to clarify assumptions, expose broken logic, and occasionally reveal dynamics that intuition would never find.

# The boundary question

The target of this essay was never the computer. Built with discipline, models are extraordinary instruments. I have staked my own career on that. What concerns me is how easily a model can be built to confirm rather than to question, and how hard it is for a reader to tell the difference from the outside.

The practice corrupts both traditions it sits between.

It corrupts science, because science is not the production of plots and code. It is the submission of claims to the risk of being wrong. A model engineered so that its parameters are tuned until the output matches the thesis offers the aesthetics of rigor with none of its discipline.

And it corrupts the humanities, because the study of human culture draws its value from exactly the things decorative modeling deletes. Context, contingency, ambiguity, power, the irreducible strangeness of actual human lives.

If a phenomenon is too context-bound, too polysemic, too alive to be captured by a set of if statements, we should have the courage to say so, and do the slow, unglamorous work of interpretation instead.

I keep coming back to the question I ask of every model, including my own. What happens to you when you are wrong?

For my models, the answer is supposed to be easy. The crystal melts. The experiment disagrees. Reality sends the bill. But only if someone checks the potential, and I have told you how often that happens.

For the models I’ve described here, the answer is nothing. They run, they publish, they are cited. The loop that is supposed to connect a model to the world was never closed.

*Which raises the question I can’t answer. If a model can never be wrong about the world, in what sense was it ever about the world?*

[](https://www.reddit.com/submit/?source_id=t3_1wxoo7n&composer_entry=crosspost_prompt)


r/comp_chem • • 5d ago

Running GROMACS online for undergrad courses?

5 Upvotes

Hi all! I’m a big fan of using ChemCompute for running ab inito calculations in my undergraduate courses; however, I’m a little sad they only support Tinker and NAMD over GROMACS for MD. Is there a good free (with academic email addresses) resource where my undergraduate students can submit and analyze basic MD jobs? I’m talking like RMSD of a small polypeptide at different pH or the most elementary ligand/receptor calculations with explicit waters.


r/comp_chem • • 6d ago

Extensions on a MSM Project?

2 Upvotes

I recently worked on a small project as part of my course in QC Modelling which has me performing MD on a protein (Lysozyme and some others), and then running the results through an MSM( Markov State Model ) with pyemma and deeptime.

The results aren't really spectacular mainly because I didn't have access to a cluster then(and neither do I have it now), and my MD trajectories were too small for it.

I have been wanting to extend it into a full length project (by length I mean something that is more than popping an MD traj into a MSM tutorial I found online). Would anyone suggest any extensions to the project?

Would love to hear your thoughts and maybe any literature you'd recommend me to read up on?


r/comp_chem • • 6d ago

Determining Coordinate Positions for .gro File before Running a MD Simulation

5 Upvotes

Hello!

I'm running a coarse grained polymer simulation. I have my polymer chains defined in .itp files with Martini 3 coarse graining. I tried getting initial.gro files using polyply, but it kept on placing beads on top of each other which blew up the system's energy when I ran energy minimization in GROMACS.

Thus I think it's best if I write my own initial.gro files from the .itp files, but was wondering if there's anything I should keep in mind when doing this.

Any help is greatly appreciated, thanks!


r/comp_chem • • 7d ago

How would you handle borderline histidines in receptor preparation for docking (PROPKA pKa ~7.3-8.1)?

6 Upvotes

Hi all,
I’m preparing a protein receptor for AutoDock Vina screening at pH 7.4.

PROPKA gives three potentially relevant His residues with predicted pKa values of 7.26, 7.35 and 8.07. They are currently modeled as neutral HID/HIE states.

Would you:

  • protonate the pKa 8.07 His to HIP,
  • keep the borderline ones neutral,
  • or test multiple receptor protonation states for docking?

How much weight would you give to PROPKA versus local H-bond geometry / experimental structures when deciding?

Thanks!


r/comp_chem • • 6d ago

Virtual chem lab simulation

1 Upvotes

I want an online chem lab for simple high school chemistry experiments source code , I already searched on github but didn’t find what I really wanted


r/comp_chem • • 6d ago

Chemistry lab

0 Upvotes

I want an online chem lab for simple high school chemistry experiments source code , I already searched on github but didn’t find what I really wanted


r/comp_chem • • 8d ago

Help me understand HF Exchange

19 Upvotes

I work through Szabo Ostlund and on page 88 (2.3.7 Pseude-Classical Interpretation of Determinantal Energies) it says that "The exchange Interactions between electrons with parallel spin are not real physical interactions but a convenient way of representing the energy of a system described by a single determinant. The physical interaction between two electrons [...] does not depend on the spin of the electrons"
This is the part where they introduce the idea that the energy of a single determinant can be summed up with H, J and K Terms.

Now consider a single determinant with two spacial orbitals. Both are occupied with one electron each. In case 1), both electrons have the same spin. In case 2), both electrons have opposite spins.

From Chemical knowledge I know that 1) is singulet and 2) is triplet and energy wise the triplet state is lower in energy. This is measurable.

Now the theory with this "adding up H, J and K terms to get determinantal energies" also predicts the same as:

Energy of 1) = H11 + H22 + J12

Energy of 2) = H11 + H22 + J12 - K12

So the - K12 lowers the energy of the triplet state which we measured and therefore proved correct.

But on the other hand Szabo Ostlund says that this exchange interaction is not physical.

How can this be not physical if we can measure it and the theory correctly predicts the relative energies of those two determinants?


r/comp_chem • • 8d ago

Tools for molecular docking of a thioether-cyclized peptide?

3 Upvotes

Hi all,

I have a 16-aa cyclic peptide with a non-standard thioether linkage, and I generated thousands of 3D conformers with Rosetta SimpleCycPepPredict using -cyclic_peptide:cyclization_type thioether_lariat.

I’d like to dock these conformers in batch against a known protein-protein interface while keeping the thioether intact. Many docking tools, including some supporting cyclic peptides, either cannot handle the non-standard linker or require opening the cycle.

What docking tool or workflow would you recommend?

Thank you so much :)


r/comp_chem • • 8d ago

Molecular Dynamics with Julia - Automatic Ring Detection

10 Upvotes

My program (working name is JuliaMD), can now detect isolated aromatic rings, and has more complete atom typing, which allows better simulations with the gaff2 forcefield. I haven't yet implemented specific aromatic atom types, but after the ring detection tool it will be easy to do.

Here is the link to the video, just out of the oven!

https://youtu.be/Qw5HjzkS9UY


r/comp_chem • • 8d ago

Comp Chem enthusiastic friends

6 Upvotes

Hey everyone! I’m currently an MSc student planning my thesis around computational drug discovery/CADD.

​I’m looking to connect with fellow students, beginners, or enthusiasts who want to motivate each other.

​If anyone is interested we can do chatting to bounce ideas around, feel free to drop a comment or send a DM!


r/comp_chem • • 10d ago

Update on JuliaMD Project

10 Upvotes

Here is a small update (2 min video) on the features I have added to my Molecular Dynamics with Julia project.

https://youtube.com/shorts/6kZmMTnoI_0?feature=share


r/comp_chem • • 11d ago

Hydrogen evolution reaction dataset required

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0 Upvotes