free-energy-perturbation

free-energy-perturbation is a skill for Claude Code from K-Dense-AI/drug-discovery-agent-skills. It costs 131 tokens per session (1,882 once invoked), scanned A, original, MIT.

A computational method for comparing how strongly related molecules bind to a protein by simulating controlled chemical changes. Free energy is a thermodynamic estimate of the binding difference between compounds, and a congeneric series is a group of molecules with a shared core.

In plain words
What is it for?
Use it to design a perturbation network between related ligands, choose atom mappings, plan Open Free Energy calculations, and review whether the results are consistent enough to guide synthesis.
Why use it?
Docking scores are rough rankings and may not reliably distinguish close alternatives. This method can provide a more rigorous ranking when deciding which compounds to synthesise, though it requires substantial computing time.

Skill for Claude Code

Written for Claude Code: allowed-tools in frontmatter. Also seen: built for openclaw.

Good fit Use it to design a perturbation network between related ligands, choose atom mappings, plan Open Free Energy calculations, and review whether the results are consistent enough to guide synthesis.

Compare 6 skills from other repositories ↓
Install with agentmods
npx agentmods add skills/k-dense-ai/drug-discovery-agent-skills/free-energy-perturbation
Install

Getting it into your agent

One page per mod, every tool's command on it. A separate URL per tool would split the same page into five that compete with each other.

Any agent
npx skills add K-Dense-AI/drug-discovery-agent-skills --skill free-energy-perturbation
Clone the repo
git clone --depth 1 https://github.com/K-Dense-AI/drug-discovery-agent-skills

Made for: Claude Code.

Wrote this? Show the measurements

A badge with what this costs and how it scanned, read live from this page, so it follows the numbers instead of freezing them. Markdown for a README, HTML for a documentation site or a project page.

agentmods badge for free-energy-perturbation

README.md
[![agentmods](https://agentmods.dev/badge/skills/k-dense-ai/drug-discovery-agent-skills/free-energy-perturbation/github.svg)](https://agentmods.dev/skills/k-dense-ai/drug-discovery-agent-skills/free-energy-perturbation)
Your own site
<a href="https://agentmods.dev/skills/k-dense-ai/drug-discovery-agent-skills/free-energy-perturbation"><img src="https://agentmods.dev/badge/skills/k-dense-ai/drug-discovery-agent-skills/free-energy-perturbation/github.svg" alt="Measured on agentmods" height="20"></a>

Or the 80×15 button, for a site that already has a row of RSS and ATOM ones. Only the verdict fits; the numbers stay here.

agentmods 80×15 button for free-energy-perturbation

Your own site · 80×15
<a href="https://agentmods.dev/skills/k-dense-ai/drug-discovery-agent-skills/free-energy-perturbation"><img src="https://agentmods.dev/badge/skills/k-dense-ai/drug-discovery-agent-skills/free-energy-perturbation.svg" alt="Reviewed on agentmods" width="80" height="20"></a>
Per session 131 Skills are progressive disclosure: only the name and description are preloaded; the body loads when the skill is used.
When invoked 1,882 The whole file, excluding the scripts and references it only reads on demand.
Security scan A 0 findings. A grade says what 26 rules found in the file — not that it is safe. Third-party audits
  • NVIDIA SkillSpector warn 7 Sept 2026
SkillSpector: 1 finding, up to medium

These are SkillSpector’s own severities. On a checked sample its high-severity flags on skills were ~96% false positives — a documented command, a public API, a “never do X” rule — so we show them as a caution to read, not a verdict. Why →

  • medium analysis-evasion · line 1
    Suspicious Unicode normalization or mixed-script content
    Fix: Review the flagged content for security risks. Ensure no credentials, secrets, or sensitive data are exposed.
How audits are shown
Origin original No closer match found in the catalogue.
Token cost

What it costs to keep this loaded

Counted locally with the o200k_base tokenizer, which is exact for GPT models; Claude uses its own tokenizer and its counts differ. Treat this as one consistent yardstick across the catalogue rather than a bill. Prices are per million input tokens.

ModelPer sessionOnce invoked
Fable 5.1 $0.00131 $0.01882
Opus 5 $0.00066 $0.00941
Sonnet 5 $0.00026 $0.00376
Haiku 4.5 $0.00013 $0.00188

Measured 12d ago against content hash 08c5edf3fbaa, method: parsed. Prices are Anthropic first-party input rates as of 2026-09-12, from the pricing page.

Security

Grade A, and why

free-energy-perturbation scanned grade A with 0 findings against 26 rules in 11 categories — prompt injection, anti-refusal, data exfiltration, privilege escalation, supply chain, agent snooping, system-prompt leakage, SSRF and excessive agency — measured 12d ago.

The scan reads SKILL.md. This mod also ships 2 executable files (scripts/fep_network.py, scripts/fep_report.py), listed below but not scanned — reading those needs a real analyzer, not pattern matching.

A static scan of the body, not an audit. Every finding is printed with the line that produced it so you can judge whether it matters here. A mod is markdown that instructs an agent; that is exactly why what it instructs is worth reading.

Nothing flagged

None of the 26 patterns this scan looks for appear in this file: no shell pipes, no recursive deletes, no credential paths, no hidden text, no instruction-override or anti-refusal phrasing, no agent-config snooping. That is not a guarantee, it is the absence of the things that are checkable.

skills/free-energy-perturbation/SKILL.md · 163 lines

How it starts

The opening of the file, as written. The whole thing — 163 lines — stays where its author put it; the contents beside it link to each section on GitHub.

Alchemical Free Energy

The rigorous end of affinity prediction. Where a docking score is a heuristic that correlates weakly with potency, FEP computes a real thermodynamic quantity from statistical mechanics — including entropy and explicit water — and reaches about 1 kcal/mol RMSE on a congeneric series. It costs GPU-days for tens of compounds, which places it precisely: immediately before synthesis, choosing which twenty analogues to make.

Tool: OpenFE 1.12, MIT. pip install openfe fetches an unrelated 0.0.12 placeholder — install from conda-forge, docker, or singularity. An NVIDIA GPU is effectively mandatory. Checked against: v1.12, June 2026.

Read references/openfe-setup.md before your first run, references/network-design.md before committing GPU time, and references/interpreting-fep.md before quoting a number — that one is judgement, not syntax.

The two scripts

Script Answers
fep_network.py What shape is the network, can it be validated, and what will it cost?
fep_report.py Do the results hang together, and what do they say?

Install the right package

mamba create -n openfe -c conda-forge openfe

PyPI's openfe is a placeholder at version 0.0.12 with no relation to this toolkit. Checked live; it is the first thing that goes wrong.

A star map cannot be checked

This is the thing to get right. Free energy is a state function, so the sum around any closed loop must be zero. It never is, and the deviation is a direct measure of the error that assumes nothing — no experimental data, no reference, no error model.

A star map has no cycles, so it forfeits the only internal validation FEP offers:

python skills/free-energy-perturbation/scripts/fep_network.py plan --ligands a,b,c,d,e --shape star
# 5 ligands, 4 edges, 0 independent cycle(s)
# no cycles: this network has NO internal error check.
# every result is relative to `a`. A bad reference corrupts the whole map.

Read the full file on GitHub · 163 lines

Files

What ships with it

5 files beside SKILL.md in the same directory: the scripts, references and assets a skill reads on demand. Not counted in the per-session cost; read them before you install if any of them is executable.

Changes

What this file has done since we first saw it

Hashed on every crawl. A supply-chain change to an agent config is a question of when, not whether, so the history is kept rather than the latest state alone.

  1. 12d ago First seen · 163 lines · 131 tokens per session scan A 08c5edf3fbaa

Subscribe to this mod's changes

free-energy-perturbation is a skill published in the GitHub repository K-Dense-AI/drug-discovery-agent-skills (28 stars, last pushed 5d ago), licensed MIT. It adds 131 tokens to every session and 1,882 once invoked, about $0.0007 per session on Opus 5. A static security scan graded it A with 0 findings. No closer match exists in the catalogue, so it is treated as the original; first seen 2026-08-30.