Table 1.
Thermostabilizing interactions
| Thermostabilizing interactions | Interaction∗ | Ptotal (%)†Cμ-Cμ | Ptotal (%)†Cν-Cν | Pmin (%)†‡Cμ-Cμ | Pmin (%)†‡Cν-Cν |
|---|---|---|---|---|---|
| Salt bridges | DE-KR | 0.7 | 1.7 | 0.6 (3) | 1.2 (1) |
| D-KR | 5.5 | — | 3.1 (2) | — | |
| E-KR | 1.4 | 6.1 | 1.1 (1) | 8.5 (2) | |
| DE-R | 2.4 | 4.6 | 3.4 (3) | 2.4 (2) | |
| D-R | 8.6 | 5.5 | 4.6 (1) | 6.3 (1) | |
| E-R | 2.6 | 2.5 | 1.1 (2) | 1.9 (5) | |
| E-H | — | 2.7 | — | 3.7 (1) | |
| Cation-π interactions | KR-FWY | 3.7 | 2.8 | 3.1 (4) | 1.6 (3) |
| R-FWY | 6.4 | 8.4 | 3.1 (2) | 5.0 (3) | |
| KR-W | 3.6 | 2.9 | 1.9 (3) | 0.3 (1) | |
| KR-Y | 3.6 | 3.5 | 1.2 (2) | 1.3 (3) | |
| K-F | — | 0.3 | — | 0.8 (2) | |
| K-Y | 8.9 | — | 3.1 (2) | — | |
| R-W | 1.8 | — | 7.3 (1) | — | |
| R-Y | 0.5 | 1.5 | 0.8 (2) | 0.7 (4) | |
| H-F | 2.6 | — | 0.8 (1) | — | |
| Aromatic interactions | F-FWY | 8.0 | 8.2 | 7.5 (1) | 9.4 (1) |
| F-W | 1.5 | 2.3 | 2.2 (2) | 4.2 (2) | |
| Negatively charged-Y or -W | DE-W | 4.1 | 1.2 | 2.6 (5) | 0.7 (2) |
| DE-Y | 3.3 | 6.1 | 1.2 (4) | 1.1 (2) | |
| D-W | 6.0 | — | 1.4 (1) | — | |
| D-Y | 8.5 | — | 0.8 (5) | — | |
| Small-charged | AG-KR | 1.2 | 1.4 | 0.7 (1) | 0.3 (2) |
| G-KR | 3.1 | 1.1 | 5.8 (2) | <0.1 (2) | |
| AG-R | 0.4 | 4.0 | 0.7 (3) | 0.6 (1) | |
| G-H | 9.1 | 5.8 | 8.1 (1) | 6.1 (1) | |
| G-R | 2.8 | 5.7 | 0.5 (5) | 0.4 (1) | |
| AG-E | 8.2 | — | 6.8 (1) | — | |
| A-E | 0.8 | — | 0.4 (2) | — | |
| Cysteine-uncharged | C-AILV | 9.7 | — | 5.7 (3) | — |
| C-AG | — | 7.8 | — | 9.1 (3) | |
| C-G | 2.4 | 5.6 | 9.0 (2) | 2.6 (4) | |
| C-FWY | 0.4 | 0.8 | 0.2 (2) | 0.4 (3) | |
| C-NQST | 7.8 | — | 9.7 (2) | — | |
| Isoleucine-hydrophobic or -small | I-AILV | 1.0 | 0.8 | 2.1 (2) | 0.9 (1) |
| I-I | 0.2 | 0.2 | 0.1 (4) | 0.1 (5) | |
| I-AG | 2.6 | 1.9 | 3.0 (2) | 6.1 (3) | |
| I-A | 0.1 | 0.1 | 1.7 (2) | 1.8 (2) | |
| I-FWY | — | 4.1 | — | 1.2 (3) | |
| I-W | 5.6 | 4.2 | 0.7 (1) | 0.6 (1) | |
| I-Y | 3.7 | 3.8 | 4.6 (2) | 4.3 (1) | |
| Methionine-charged, aromatic, or -small | M-KR | 3.7 | 1.2 | 4.4 (1) | 4.5 (2) |
| M-DE | — | 3.5 | — | 4.9 (3) | |
| M-FWY | 7.6 | 6.3 | 7.0 (2) | 5.1 (1) | |
| M-Y | 6.60 | 6.10 | 2.2 (1) | 2.6 (1) | |
| M-A | 1.1 | 1.2 | 2.1 (3) | 1.7 (3) | |
| Others | Y-AILV | 5.7 | 3.5 | 5.7 (1) | 4.9 (1) |
| Y-V | 9.3 | — | 1.8 (3) | — | |
| R-KR | 6.2 | — | 6.7 (1) | — | |
| E-N | — | 4.1 | — | 6.0 (2) | |
| R-N | 2.1 | — | 1.5 (3) | ||
| V-KR | 9.4 | — | 3.6 (2) | — | |
| F-P | 7.9 | 3.1 | 8.8 (1) | 3.0 (3) | |
| N-P | 5.0 | — | 1.4 (2) | — | |
| T-Y | — | 3.9 | — | 3.2 (1) |
Italic indicates unfavorable interactions, for which the folding free energy is always positive.
Ptotal and Pmin are the probabilities (%) that a similar difference in free-energy profile will be observed in random protein subsets. Ptotal is defined with respect to the global surface area between ΔWs from thermostable and mesostable subsets, and Pmin is defined with respect to the surface area around the free-energy minima (see Appendix S2 in the Supporting Material and Fig. S1). A dash means that the statistical significance criterion (Ptotal < 5% and Pmin < 10% in the case of pairs of amino acid groups, and Ptotal < 10% and Pmin < 20% in the case of single amino acids) is not satisfied.
Number of local minima considered is given in parentheses.