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. Author manuscript; available in PMC: 2015 Jul 3.
Published in final edited form as: Mol Biosyst. 2014 Apr 29;10(7):1890–1904. doi: 10.1039/c3mb70620f

Figure 9.

Figure 9

QM/MM results for proposed pathways in figure 8 for the EGFR TKD/ATP/Y1068 peptide ternary complex. (A)&(D): Pathway I, dissociative mechanism; (B)&(E): Pathway I, associative mechanism; and (C)&(F): Pathway II, associative mechanism. R = reactant; P = product; and TS = transition state characterized by a trigonal bipyramidal geometry about Pγ. (A–C) Distributions of values for the nucleophilic attack distance, λa (distance between the tyrosine oxygen and the ATP Pγ) and the bond cleavage distance, λc (distance between the ATP Pγ and ATP O2/3β) along the reaction pathways. (D–F) Energy changes along the reaction pathways in QM/MM simulations for the different mechanisms. In the energy landscape in panel D, the first peak corresponds to the formation of the trigonal-bipyramidal transition state where the proton from the tyrosine hydroxyl has been dissociated, while the second peak corresponds to the proton migrating to the ADP molecule.