Annals of the New York Academy of Sciences, Vol 482, Issue 1 222-233, Copyright © 1986 by New York Academy of Sciences
Dynamic simulations of oxygen binding to myoglobin
D. A. Case and J. A. McCammon
We report dynamic simulations of the process by which a dioxygen molecule
enters or leaves the heme pocket region of myoglobin along a path between
the distal histidine (E7) and valine (E11). Our reaction coordinate
measures the distance of the ligand from a "dividing plane" defined by
three protein atoms. The equilibrium probability distribution as a function
of this coordinate is determined by a series of molecular-dynamic
simulations with overlapping "umbrella" constraining potentials; the
resulting potential of mean force has a barrier of about 7 kcal/mol for
exit from the heme pocket. A comparison of this free energy profile with
the corresponding potential energy profile suggests that entropy effects
dominate the kinetic barrier. Reactive trajectories are generated from
dynamic simulations beginning at the top of the potential of mean force;
only a small fraction of these recross the dividing surface, indicating
that transition state theory may be a good approximation for this process.
