Mechanisms for Benzene Dissociation through the Excited State of T4 Lysozyme L99A mutant (Biophysical Journal)

The atomic-level mechanisms that coordinate ligand release from protein pockets are only known for a handful of proteins. Here, we report results from accelerated molecular dynamics (aMD) simulations for benzene dissociation from the buried cavity of the T4 lysozyme Leu99Ala mutant (L99A). In these simulations, benzene is released through a previously characterized sparsely populated room temperature excited state of the mutant, explaining the coincidence for experimentally measured benzene off rate and apo protein slow timescale NMR relaxation rates between ground and excited states.