Table 3.
Hot spot prediction for the mdm2–p53 interface
| P53 | mdm2 | ||||
|---|---|---|---|---|---|
| Residue | ΔΔGbind predicted, kcal/mol | No. of allowed substitutions (peptide) | Residue | DDGbind predicted, kcal/mol | Contacts p53 residues |
| E17 | −0.17 | 19 | I 30 | 0.97 | W23 |
| T 18 | −0.02 | 13 | L 33 | 0.29 | W23 |
| F 19 | 3.85 | 1 | I 37 | 0.90 | F19, W23 |
| S 20 | 0.15 | 7 | M 38 | 0.51 | S20 |
| D 21 | 0.00 | 6 | Y 43 | 1.23 | F19 |
| L 22 | 1.06 | 3 | Q 48 | 1.39 | T18, F19 |
| W 23 | 4.54 | 1 | V 69 | 1.21 | F19, L22 |
| K 24 | −0.02 | 15 | K 70 | 0.06 | E17 |
| L 25 | 0.00 | 14 | L 75 | 0.82 | L26 |
| L 26 | 2.04 | 1 | Y 76 | 1.37 | L26 |
All residues in the p53 peptide fragment and mdm2 residues contacting the peptide were computationally replaced by alanine. The number of allowed substitutions was taken from ref. 21 and reflects the number of different amino acids that could be individually substituted at each position in a phage display selected peptide similar to the p53 fragment without significant loss in binding affinity. Predicted hot spot residues are shown in bold type.
*
Residues in bold type are p53 hot spots (see left half).