1730 J. Chem. Inf. Model., Vol. 50, No. 9, 2010 CHAN AND LABUTE Figure 5. The 13 ligands of the p38 system. Next we considered the repulsion term between hydrogen- bonding atoms and hydrophobic atoms (T4 and T5 in Table 1). We continued to test both schemes for deﬁning hydrophobicity. Results are given in Tables 2e and 2f. Here we see that the ﬁrst scheme of deﬁning hydrophobicity was slightly better and that the optimal weight for the repulsion term, wR1, was around -1.0. So we chose to deﬁne hydrophobic atoms simply using the MOE deﬁnition. After this we investigated a repulsion term between hydrogen-bond donor and acceptor atoms (T6 and T7 in Table 1). Naturally, atoms that can be both donor and acceptor were excluded from consideration. Perhaps surprisingly, it was found that this term did not seem to improve the scoring function (see Table 2g). So these terms were dropped from the scoring function. Finally the projected acceptor and donor feature points were considered (T8 and T9 in Table 1). These points correspond to the expected positions of donors and acceptors on the binding pocket. In this sense they are different from the previously considered terms that are atom based. So we tried out different values of R as well as different weights, wPF, for this term. The results are given in Table 2h. It can be seen that an Rp value of 0.125 Å-2 coupled with a weight of 2.0 was a good combination. Otherwise an Rp value of 0.0625 Å-2 coupled with a weight of 1.0 was also respectable.