Fig. 4.

Training of the couplings during the IPA. Residue pairs comprising an HK site and an RR site were scored by the Frobenius norm (i.e., the square root of the summed squares) of the couplings involving all possible residue types at these two sites. The best-scored residue pairs were compared with the 27 HK−RR contacts found experimentally in ref. 27. Solid curves show the fraction of residue pairs that are real contacts (among the k best-scored pairs for four different values of k) versus the iteration number in the IPA. Dashed curves represent the ideal case, where, at each iteration, $N_{\text{increment}}$ randomly selected correct HK−RR pairs are added to the CA. The overall fraction of residue pairs that are real HK−RR contacts, yielding the chance expectation, is only $3.8\times {10}^{-3}$. The IPA is performed on the standard dataset with $N_{\text{increment}}=6$, and all data are averaged over 500 replicates that differ in their initial random pairings.