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.
FlexAID∆S 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. FlexAID∆S 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 ∆G claim.
FlexAID∆S 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 ∆Gbind 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 ∆S.
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