Table 1.
An overview of the calculated interaction energies (kcal/mol) between key sub-structures and residues in A) B-RAFWT and B-RAFV600E and in B) B-RAFK601E and B-RAFD594V.
| A) | B-RAFWT | B-RAFV600E | ||||
| Substructure | vdW | El | Total | vdW | El | Total |
| A-loopa | -100.9 ± 6.9 | -200.1 ± 18.6 | -301.0 ± 16.5 | -99.1 ± 5.6 | -153.6 ± 24.4 | -252.7 ± 24.5 |
| A-loop-αC-helixb | -20.2 ± 1.9 | -31.4 ± 5.9 | -51.6 ± 5.4 | -27.0 ± 3.2 | -5.8 ± 10.6 | -32.8 ± 9.9 |
| A-loop-P-loopc | -12.7 ± 2.2 | -18.2 ± 5.5 | -30.9 ± 5.1 | -22.6 ± 2.0 | -11.9 ± 2.8 | -34.5 ± 3.2 |
| A-loop-β6-strandd | -12.4 ± 2.7 | -31.6 ± 8.6 | -44.0 ± 8.4 | -14.2 ± 2.1 | -44.5 ± 9.3 | -58.7 ± 8.9 |
| A-loop-F-loope | -18.5 ± 1.8 | -3.4 ± 4.4 | -21.9 ± 4.1 | -15.3 ± 2.7 | -20.3 ± 23.5 | -35.6 ± 23.4 |
| A-loop-αG-helixf | -3.6 ± 1.3 | -33.6 ± 7.4 | -37.2 ± 7.3 | -0.7 ± 0.3 | -6.4 ± 2.5 | -7.1 ± 2.6 |
| Lys601g | -14.9 ± 2.3 | -150.3 ± 15.1 | -165.2 ± 14.8 | -15.8 ± 2.3 | -137.7 ± 12.7 | -153.5 ± 12.1 |
| Lys601-αC-helixh | -0.7 ± 1.5 | -73.3 ± 9.9 | -74.0 ± 9.2 | -3.2 ± 0.5 | -22.8 ± 3.1 | -26.0 ± 3.1 |
| Lys483-Asp594i | -0.1 ± 0.9 | -69.0 ± 9.5 | -69.1 ± 9.0 | -0.3 ± 0.1 | -39.4 ± 4.4 | -39.7 ± 4.5 |
| Lys601-Asp594j | -0.2 ± 0.6 | -58.2 ± 4.2 | -58.4 ± 4.0 | -1.5 ± 3.9 | -61.5 ± 4.5 | -63.0 ± 3.4 |
| (K601-D594)-k (E501-K483) |
-0.9 ± 1.7 | -70.8 ± 7.5 | -71.7 ± 6.7 | -4.0 ± 0.5 | 0.2 ± 3.5 | -3.8 ± 3.5 |
| (K601-D594)-l (D576-N581) |
-1.4 ± 0.4 | 2.3 ± 3.3 | 0.9 ± 3.1 | -2.1 ± 1.5 | -40.3 ± 8.7 | -42.4 ± 8.1 |
| B) | B-RAFK601E | B-RAFD594V | ||||
| Substructure | vdW | El | Total | vdW | El | Total |
| A-loopa | -117.7 ± 5.8 | -261.5 ± 26.4 | -379.2 ± 26.6 | -105.6 ± 5.3 | -108.8 ± 12.2 | -214.4 ± 12.8 |
| A-loop-αC-helixb | -34.2 ± 2.9 | -9.2 ± 12.2 | -43.4 ± 12.2 | -32.7 ± 2.7 | -27.7 ± 7.9 | -60.4 ± 7.6 |
| A-loop-P-loopc | -16.2 ± 1.8 | -18.4 ± 3.8 | -34.6 ± 4.4 | -20.0 ± 1.7 | -1.9 ± 2.4 | -21.9 ± 2.9 |
| A-loop-β6-strandd | -17.9 ± 2.2 | -26.9 ± 7.1 | -44.8 ± 7.2 | -18.5 ± 2.4 | -35.1 ± 7.7 | -53.6 ± 7.0 |
| A-loop-F-loope | -2.6 ± 0.7 | -0.2 ± 1.6 | -2.8 ± 1.8 | -13.9 ± 2.6 | 1.1 ± 3.7 | -12.8 ± 5.0 |
| A-loop-αG-helixf | -2.3 ± 1.2 | -56.5 ± 8.3 | -58.8 ± 8.4 | -0.07 ± 0.1 | 0.12 ± 1.7 | 0.05 ± 1.7 |
| Lys601g | -12.1 ± 2.6 | -141.6 ± 7.2 | -153.7 ± 6.8 | -20.3 ± 2.2 | -102.9 ± 12.8 | -123.2 ± 12.7 |
| Lys601-αC-helixh | -5.6 ± 1.4 | -10.8 ± 4.5 | -16.4 ± 4.1 | -5.8 ± 0.8 | -29.6 ± 3.0 | -35.4 ± 2.9 |
| Lys483-Asp594i | -0.4 ± 0.6 | -52.8 ± 7.7 | -53.2 ± 7.5 | -0.02 ± 0.0 | 1.06 ± 0.3 | 1.04 ± 0.3 |
| Lys601-Asp594j | -0.3 ± 0.1 | 36.4 ± 3.4 | 36.1 ± 3.3 | -0.8 ± 0.7 | -6.6 ± 1.9 | -7.4 ± 1.7 |
| (K601-D594)-k (E501-K483) |
-2.0 ± 1.4 | -48.9 ± 5.7 | -50.9 ± 5.5 | -4.0 ± 0.6 | -9.1 ± 2.1 | -13.1 ± 2.0 |
| (K601-D594)-l (D576-N581) |
-2.9 ± 0.5 | 60.9 ± 4.2 | 58.0 ± 4.0 | -2.6 ± 1.5 | -79.0 ± 6.8 | -81.6 ± 6.7 |
aThe interactions between the A-loop (residues 593–623) and the remaining protein. b, c, d, e, fThe interactions between the A-loop and the αC-helix (residues 492–506), the P-loop (residues 462–471), the β6 strand (residues 571–578), the F-loop (residues 625–634) and the αG-helix (residues 660–672), respectively. g, h The interactions between Lys601 and the remaining protein, and Lys601 and the αC-helix, respectively. i The interactions between Lys483 and Asp594. jThe interactions between Asp594 and Lys601.k, l The interactions between the Asp594-Lys601 and Lys483-Glu501 ion pairs and the Asp594-Lys601 and Asp576-Asn581 pairs, respectively.
The van der Waals and the electrostatic contributions to the total interactions energies averaged for the period 10–15 ns of simulation time, along with the measured standard deviations, are listed.