This information gap to generate clinically relevant annotation can be bridged using physics-based biomarker Chapter paring, where parallel simulations can model multiple clinical variants en masse. From these physics and ML driven calculations, sequence-function relationships can be established to generate promising target candidate profiles (TCPs) and accelerate drug discovery. Accounting for the ensemble of structures a protein adopts in solution with computer simulations overcomes many of the limitations imposed by assuming a single protein structure, and can scale to study many variants that may be difficult to experimentally study. Furthermore, more considering protein conformational ensembles allows physics-based biomarker pairing to extrapolate to previously unseen or clinically infrequent mutations, supplementing sparse patient data.