“…This probably is as nonheme iron dioxygenases often have very rigid structures where the substrate is tightly bound (Aluri and de Visser, 2007 ; Kumar et al, 2011 ; Tchesnokov et al, 2016 ; Faponle et al, 2017 ). Previous QM/MM studies on analogous nonheme iron dioxygenases indeed reproduced experimental chemoselectivities excellently using the same methods and procedures described here (Aluri and de Visser, 2007 ; Karamzadeh et al, 2010 ; Kumar et al, 2011 ; Pratter et al, 2013 ; Quesne et al, 2014 , 2016a ; Hernández-Ortega et al, 2015 ; Tchesnokov et al, 2016 ; Faponle et al, 2017 ; Timmins and de Visser, 2017 ; Timmins et al, 2017 ; Hofer and de Visser, 2018 ). Moreover, changing the QM region, basis set or density functional method did not change the ordering of the transition states.…”