Flux-species sampling enables holistic exploration of biocircuit behavior

Biocircuit behavior is usually discovered by drawing uncertain kinetic parameters and simulating, but the scored phenotypes are functions of steady-state species, catalytic fluxes, dominance relations, and local response matrices. We introduce flux-species sampling (FSS), which samples that functional layer directly and algebraically inverts to parameters. This coordinate change turns regulatory modes into simple dominance chambers, gives every full-dimensional behavior-realizing regime positive measure, and can replace the sampling stage of existing pipelines without changing downstream stability or phenotype tests. A sequestration toy shows how a large species regime can collapse into a narrow parameter strip. In an enzymatic feedback motif, FSS rescues free-A* adaptation missed by parameter sampling and identifies the regime as non-Michaelian and complex-dominated. In MultiFate-N, FSS separates a sampling limitation from a structural limitation and rescues parameter sets realizing all 2N states. HighlightsO_LIFlux-species sampling (FSS) draws the control/function layer where biocircuit behavior is read C_LIO_LIFSS boxes intersect every full-dimensional behavior-realizing regime with positive measure C_LIO_LIFSS is no slower than parameter-space sampling and is a hot fix for existing pipelines C_LIO_LIFSS rescues non-Michaelian free-A* adaptation missed by parameter sampling C_LIO_LIFSS rescues the all-2N symmetric MultiFate regime missed by fixed parameter boxes C_LI eTOC blurbThis study reframes biocircuit exploration by sampling steady-state species and fluxes rather than raw parameters. The resulting flux-species coordinate exposes regulatory dominance regimes, rescues adaptation and multistability regimes missed by parameter sampling, and gives finite sampling nulls an explicit scope.