When interested in predictive modeling of PL systems, we are therefore faced with a painful dilemma (Figure ). An appropriate description on biochemically-relevant NCIs is, on the one hand, required; the dynamic relationship between PL pairs cannot, on the other hand, be ignored; holding on to one source of information and letting go of the other would make our inquiry simple and elegant, but wrong and unreliable; trying to hold on to both complicates things further, as reasonable interfaces between different kinds of information must be established -giving rise to many corresponding sources of error that cannot necessarily be assessed.