Decision stability of a default docking pipeline: a seed, box-placement, and protomer audit on LIT-PCBA MTORC1

Agentic and automated drug-discovery workflows increasingly call molecular docking as a black-box subroutine and act on its ranked output, typically from a single run under software defaults. We ask a narrow, operational question: if the same default pipeline is re-run with a different random seed, a slightly displaced search box, or a different input protomer, which decisions-the top-k compounds a downstream agent would advanceactually change? Using AutoDock Vina 1.2.7 on the LIT-PCBA MTORC1 target (PDB 4jsx) with a fixed, score-blind panel of 60 ligands (20 actives, 40 inactives), we predeclared the decision rule and the seed and box-placement perturbation axes against a baseline, added a protomer arm whose selection criterion was amended during execution (disclosed with dates), and compared top-12 decision sets as symmetric differences (exits and entries), Jaccard indices, and binary decision changes, with pose quality checked by PoseBusters against the exact receptor used for docking. A positive control (redocking the co-crystallized ligand, symmetry-corrected RMSD 0.647 Å) validated the setup. Changing only the random seed replaced 3 of 12 top-12 members (6/60 binary decisions changed); a 2 Å box shift along x replaced 2, along y replaced 4; protomer changes at pH 7.0 replaced none. Eight ligands accounted for all flips, and the single PoseBustersinvalid pose was also a recurrent flipper. A threeseed majority-vote consensus cost 3× compute, dropped the invalid recurrent flipper, and still disagreed with every individual run; we report it as a priced mitigation with measured residual disagreement, not as certified stabilization. All results concern decision repeatability only: nothing here establishes that any decision set is correct, and a consensus can stabilize a wrong answer. All code, inputs, checkpoints, and negative results are provided in an accompanying archive prepared for the author; no public release has been made.