Fig. 10. Differentiating between different classes of ligands. The binding site preference of different compounds was evaluated in terms of (A) the predicted binding affinities calculated for the extended ensemble in the M1 subsite, and (B) the respective populations in the M1 site. Ranking the compounds based on their binding affinities places the high-affinity modulators and the non-substrates at the two extremes, with low-affinity modulators and substrates lying between them. Comparison of the binding site population in the M1 subsite further distinguished the high-affinity modulators and small substrates (showing high populations in the M1 subsite) from low-affinity modulators and large substrates (showing higher populations in the M2 subsite instead).