Premium
Dynamic Simulations of Oxygen Binding to Myoglobin
Author(s) -
CASE DAVID A.,
McCAMMON J. ANDREW
Publication year - 1986
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.1986.tb20953.x
Subject(s) - library science , citation , foundation (evidence) , chemistry , computer science , political science , law
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.