Srinivasan Lyengar, Indiana University
One part of this talk deals with new computational methods for the simultaneous dynamical treatment of electrons and nuclei, where the electrons are treated at extremely high quantum chemical (such as CCSD) accuracy. In the second part of the talk, we discuss our recent work on the rate-determining hydrogen transfer step in the catalytic transformation of fatty acids by the enzyme Soybean Lipoxygenase-1. This enzyme is a non-heme metalloprotein and the catalytic process shows the remarkably large H/D KIE of 81. While we have studied this in the past, this talk will focus on the “computational discovery” of a new hydrogen bond (between the Fe-OH hydrogen and Ile839 on the figure above) that modulates the hydrogen transfer (transferring hydrogen shown in yellow). We find that when this hydrogen bond is “turned off” in our computational experiments, the H-transfer stops. Furthermore, this hydrogen bond also leads to the non-Arrhenius behavior that we note on the figure to the right.