On the applicability domain of HADDOCK3 for protein-aptamer docking: documented failure modes from a 5x7 cross-target screening matrix and a 1676 aa receptor ca... (opens in new tab)

We screened a 5 receptor x 7 aptamer = 35-cell cross-target matrix with HADDOCK3 [1] under blind ambiguous-interaction-restraint (AIR) protocols on AlphaFold-modelled receptors. The screen surfaced 12 operationally distinct failure modes (collapsing to about 8 conceptual classes; Section 3.1). The K_D-calibration subset is n = 4 cells with literature K_D records under matched assay conditions; the broader cohort includes >= 6 biological cognate or intended-cognate cells. The principal case st...