posted on 2023-11-09, 19:06authored byXiaoliang Pan, Richard Van, Jingzhi Pu, Kwangho Nam, Yuezhi Mao, Yihan Shao
In
enzyme mechanistic studies and mutant design, it is highly desirable
to know the individual residue contributions to the reaction free
energy and barrier. In this work, we show that such free energy contributions
from each residue can be readily obtained by postprocessing ab initio quantum mechanical molecular mechanical (ai-QM/MM)
free energy simulation trajectories. Specifically, through a mean
force integration along the minimum free energy pathway, one can obtain
the electrostatic, polarization, and van der Waals contributions from
each residue to the free energy barrier. Separately, a similar analysis
procedure allows us to assess the contribution from different collective
variables along the reaction coordinate. The chorismate mutase reaction
is used to demonstrate the utilization of these two trajectory analysis
tools.