Flexible molecular docking where genetic search meets transparent ensemble analysis—without laundering a scoring proxy into experimental thermodynamics.
NO BLACK BOX. NO FREE-ENERGY COSPLAY.
FlexAIDΔS uses entropy at distinct layers. Keeping those layers separate is the difference between information theory and thermodynamic fan fiction.
The Shannon entropy of the GA population’s energy histogram. Collapse toward a narrow basin is evidence of search concentration—not proof of physical equilibrium.
Boltzmann-weighted pose probabilities derived from the sampled ensemble. Meaning depends on the energy proxy, temperature, microstate definition, and sampling adequacy.
Elastic-network eigenmodes estimate how binding redistributes accessible motion. The tENCoM correction is relative unless its eigenvalue-to-frequency mapping is calibrated.
THE FIRST-PRINCIPLES CONNECTIONA search algorithm loses uncertainty as it finds a basin. A molecular ensemble loses accessible microstates as binding constrains motion. Both can be written with Shannon’s functional; they are analogous because both describe probability—not because they are the same physical quantity.
Move the effective temperature. At low T, probability mass collapses onto the best CF state. Raise T and more poses become statistically accessible. Entropy rises; so does the effective number of occupied states, eᴴ.
This is a transparent toy ensemble. The slider changes an effective scoring temperature, not a physical thermostat.
Search, score, ensemble, validate. Each layer has a job, a boundary, and a failure mode. FlexAIDΔS keeps the ledger visible.
Genetic search traverses pose, torsion, ring-conformer, and side-chain degrees of freedom across configurable restarts.
GA / flexible DoF / diversity controlsA Voronoi contact function ranks geometric and chemical complementarity during search. It is a scoring proxy—not measured affinity.
Vcontacts / CF / OpenMP + SIMDPost-search analysis computes log Z, F, ⟨E⟩, S, Cᵥ, Boltzmann weights, clusters, and optional vibrational corrections.
StatMech / BindingMode / tENCoMRMSD admission, official PoseBusters bridging, tENCoM diagnostics, pinned provenance, and protocol-defined election test the claim.
RMSD / bust / benchmark contractsThe TUI exposes the trajectory rather than decorating the endpoint: population diversity, Shannon collapse, the elected pose boundary, and validator receipts remain separate events.
$ [init] 256 chromosomes · 14 flexible DoF · seed=random› _Animated interface demo with synthetic values—not a benchmark receipt or an experimental ΔG claim.
FlexAIDΔS explicitly separates the elected-pose result from sampling ceilings. STRICT/claim_ready is the headline contract; S1, S2, and S3 remain diagnostics. Native-pose seeding is forbidden on claim runs. A contact score is never silently relabelled as experimental binding free energy.
Inspect benchmark contractsEnsemble-derived F is a model estimate. It becomes an experimental ΔGbind claim only after the complete thermodynamic path and calibration have been validated for that use.
Shannon’s functional is the mathematical bridge, not a licence to merge unlike quantities. Every layer below states what is computed, what the result can mean, and where the implementation lives.
A histogram of population CF scores, reported in nats. Collapse means the search has concentrated its score distribution; it is not a molecular entropy or a physical ΔS.
Inspect implementationBoltzmann-like reweighting uses CF and an effective T*. Its F* is an internally defined free-energy analogue in proxy units—not a calibrated experimental binding free energy.
Inspect implementationENCoM supplies a stiffness-like mode spectrum. Absolute vibrational entropy requires a documented eigenvalue-to-frequency calibration; otherwise the result remains in relative model units.
Read calibration contractHeadline success is STRICT/claim_ready only: frozen denominator, exact elected pose, official PoseBusters, complete tENCoM/Eigen receipts, and protocol-eligible provenance.
Read admission contractC++26 engine. Python analysis API. PyMOL integration. Reproducible campaign runner. Apache-2.0, because a scientific instrument should survive inspection.
brew tap lebonhommepharma/flexaidds https://github.com/LeBonhommePharma/FlexAIDdS
brew install lebonhommepharma/flexaidds/flexaidds