Electrostatic mechanism of V600E mutation-induced B-Raf constitutive activation in colorectal cancer: molecular implications for the selectivity difference between type-I and type-II inhibitors.

Abstract excerpt

The oncogenic mutation V600E in B-Raf activation loop (A-loop) has been frequently observed to cause drug resistance in colorectal cancer chemotherapy. Here, the molecular mechanism of V600E-induced conformational flipping of B-Raf activation loop (A-loop) is investigated systematically via continuum electrostatic analysis. It is found that substitution of the electroneutral Val600 residue with negatively charged...

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