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Le Bonhomme Pharma

We’ve been told to say NO to drugs. Bonhomme disagrees. ALL IN psychopharmacology — open-source, thermodynamically rigorous, unapologetically pro-drug in the clinical sense that matters.

Explore FlexAIDΔS Read the Manifesto

Free-energy ledger. With ΔH held at −16.0 kcal/mol and ΔS at −22.0 cal per mol per kelvin, the entropy penalty −TΔS grows from +4.4 to +7.7 kcal/mol as temperature rises from 200 K to 350 K, so ΔG moves from −11.6 to −8.3 kcal/mol. Enthalpy buys binding; entropy takes its cut, and the cut scales with temperature.

Illustrative ledger · ΔH and ΔS held fixed (ΔS = −22.0 cal·mol−1·K−1) · T sweeps 200 → 350 K · ΔH, −TΔS, ΔG in kcal/mol

FlexAIDΔS pipeline

  1. 01Targetbinding-site cleft
  2. 02DockGA conformational search
  3. 03Scoresoft complementarity
  4. 04Ranktop-scoring poses
  5. pose & affinity
  • −TΔSEntropy Term · Never Dropped
  • 60+Psychoactives Profiled
  • 12Works On This Page
  • Apache 2.0By Construction

See it run

FlexAIDΔS, From the Terminal

Illustrative session — the flexaidds CLI driving the FlexAIDΔS engine on one Astex target: load, cleft, search, cluster, write. Process, not results: timings and scores are synthetic, and benchmark figures wait for the preprint.

Illustrative transcript of one synthetic FlexAIDΔS docking run: the flexaidds command, the engine banner, receptor and ligand loading, cleft and grid setup, a genetic-algorithm search whose best score improves and whose population entropy collapses over 500 generations, clustering into binding modes, the entropy and enthalpy terms, and poses written to disk with a receipt. No benchmark figure appears anywhere in it.

lp@bonhomme:~/flexaidds$ flexaidds dock --receptor astex85/1s3v/rec.pdb --ligand astex85/1s3v/lig.mol2 --entropy shannon --temp 310 --seed 7 --out runs/1s3v
FlexAIDΔS 2.0.3 · entropy-driven docking · commit 2a60f65 · backend metal (fp64 thermodynamics on CPU)
ΔG = ΔH − TΔS T = 310 K entropy shannon · Boltzmann weights from CF
[00:00.02] receptor astex85/1s3v/rec.pdb · 1602 heavy atoms · 12 flexible side chains
[00:00.06] ligand astex85/1s3v/lig.mol2 · 24 heavy atoms · 5 torsions · SYBYL typed
[00:00.11] pocket GetCleft · cleft 1/3 · 38 lining residues
[00:00.40] grid spacer 0.375 Å · CF matrix MC_st0r5.2_6.dat · 40 × 40 SYBYL types
[00:00.55] search GA (gaboom) · 500 chromosomes × 500 generations · FLEXAID_SEED=7
gen best CF mean CF S_pop/nats
100 −101.8 −67.0 3.92
200 −117.2 −88.5 2.79
300 −123.5 −99.6 2.24
400 −125.8 −105.3 1.97
500 −126.8 −108.2 1.84
[00:12.69] cluster FOPTICS · 20 poses → 6 binding modes · CF basins
[00:12.82] entropy ΔS · Shannon over the 20-pose ensemble · S = 1.21 nats
[00:12.87] entropy ΔS_vib · tENCoM normal modes · 5 torsions
[00:12.95] score ΔH · Vcontacts Voronoi CF · GPU batch · 20 poses
[00:13.02] elect ΔG · mode 1 of 6 · best CF −126.8 · 5 poses in basin
[00:13.09] write runs/1s3v/mode_01..06.pdb · thermo REMARKs · receipt.json · engine_sha 5ecbb89e
[00:13.11] done status=ok · rc=0 · 6 modes · 20 poses · 13.11 s wall
lp@bonhomme:~/flexaidds$

Open-source arsenal

What We Build

Pharmacology

Docking engine

FlexAIDΔS

Entropy-driven molecular docking. The full ΔG = ΔH − TΔS with Shannon entropy — torsional ENCoM, Voronoi contact function, GPU batch scoring.

Explore FlexAIDΔS
Product docs

Entropy-Driven

The full FlexAIDΔS entropy-driven docking landing — architecture, benchmarks, install, modules and live repository stats. One kernel, refracted into a family of works.

Read the docs
Slide deck

Benchmark

One equation, three benchmark sets, an engine you can rerun. The deck walks the protocol on Astex Diverse, Astex Non-Native and HAP2 — inputs, settings and seeds — so any figure it shows can be rerun rather than taken on faith.

View the benchmarks
Source

The Engine

Every claim on this page is meant to be checked, so the code is the artefact. Clone the engine, rerun the protocol on your own targets and diff the receipts against ours.

Read the source (opens in a new tab)
Harm reduction

Drug of the Day Rotates daily By mechanism

A different compound every day. Rigorous pharmacology plus entropy-docking commentary. Mechanism over moralising.

Open Drug of the Day 
Reference

Periodic Table

The periodic table of psychoactive compounds — pharmacological classes, receptor targets and structural families. The reference sheet your professor wouldn’t give you.

Open table

Beyond pharmacology

Entropy toolkit

Shannon

Entropy-collapse detector for frontier LLM agents. Zero-shot evaluation-awareness and strategic-deception monitoring via the same H = −Σ pi log2 pi kernel that powers binding and HRV.

Explore Shannon
Remaining work

Exergy App Store release in preparation

Usage tracker for Claude, Codex, Cursor, and Grok — Mac menu bar, iPhone, iPad, Watch. OAuth. Private iCloud. Tokens stay on device. Shannon watches entropy collapse; Exergy watches how much quota you have left to spend.

Meet Exergy
Biofeedback

NATURaL App Store release in preparation

Free guided chair yoga for iPhone and iPad, with an Apple Watch companion. On-device session history and optional Apple Health integration. Experimental entropy indicators, with their limits made explicit.

Meet NATURaL
Interactive

Entropy Docking

Shannon × Music × Molecular, in AR/VR. BPM drives temperature, Crooks cycles, HRV coupling and binding entropy collapse — click to play in-browser.

Launch experience
Instrument analysis

Symphony

Pitch and spectrum from the live microphone. Log-Hz axis, peak-picking across 27.5–5000 Hz, density-clustered tracks and note names over all 88 keys. The page listens and never plays back — and it never fakes a tune.

Open Symphony
Keyboard board

Piano-crayon

The crayon keyboard from Symphony, on its own page. Pick US ANSI or Canadian French CSA and one board remaps instantly; keys light as they are struck, ten fingers at a time, with extras only when they cluster cleanly.

Open Piano-crayon
GTFS atlas

Rive

Public-transit atlas for Québec, Montréal, Sherbrooke and Trois-Rivières, built from the agencies’ official GTFS feeds. Reads the next departures at a stop you are not standing at — map, route shapes, and walk-plus-transit trips with one transfer. Free, no subscription, Apache 2.0.

Open Rive

Operating principles

The Physics First

01 Thermodynamics

ΔG = ΔH − TΔS

Every binding event is a thermodynamic equation. Ignoring the entropy term isn’t a shortcut — it’s a wrong answer. We compute the whole thing.

02 Open science

Apache 2.0, Full Stop

Proprietary docking tools gatekeep science behind paywalls. Drug discovery belongs to everyone. Our code ships under Apache 2.0, reproducible by construction.

03 Harm reduction

Education Over Prohibition

The war on drugs failed the pharmacology exam. Psychoactives are tools with mechanisms — understandable, predictable, teachable. We teach them.

04 Mechanistic rigor

No Black Boxes

ML correlation without mechanism is astrology with better marketing. We use neural networks as a last resort, not a first instinct. First principles, every time.

Manifesto

The psychiatric system isn’t broken — it was built for a different century. We’re building the tools for this one.

Open-source. Thermodynamically rigorous. Unapologetically pro-drug in the clinical sense that matters: every molecule is a hypothesis about biology, and the stigma attached to psychoactives has killed more people than the molecules themselves.

From the statistical mechanics of ligand binding to the social mechanics of harm reduction, the physics is the same: systems seek lower free energy. Our job is to lower the barrier — algorithmically, pharmacologically, politically.

“Drug is ALWAYS an answer — sometimes the only one available.”

— @BonhommePharma

Founder

Louis-Philippe (LP) Morency

PhD Candidate · Psychopharmacology · Université de Montréal · Le Bonhomme Pharma

Built FlexAIDΔS because the field needed thermodynamically honest docking and nobody else was going to do it from a basement in Little Burgundy. Main coder on FlexAIDΔS, Shannon, ClusterFuck and NRGsuite.

Shannon entropy and cats. Anti-prohibitionist. Writing a book on housing, organized crime, and harm reduction in Montréal.

CV → Résumé → @LeBonhommePharma (opens in a new tab) lp@thebonhomme.com NRGlab · UdeM (opens in a new tab)