Binding Free Energy Calculations of the BRAF Dimer Complexes with Vemurafenib and PLX7904.

<p>Binding free energies and alanine scanning of the binding site residues in the drug-bound monomer of the Vemurafenib-BRAF complex (A) and the PLX7904-BRAF complex (B). The standard errors of binding free energy differences, which are the standard deviation of the mean values, were ~ 0.15–0.25 kcal/mol for the Vemurafenib-BRAF complex and 0.2–0.3 kcal/mol for the PLX7904-BRAF complex. A close-up of the Vemurafenib binding mode (C) and PLX7904 binding mode (D). The inhibitor is shown in atom-colored sticks and annotated. The binding site residues are shown in orange sticks and annotated.