THE BARRIER FOR HEME-PROTEIN SEPARATION ESTIMATED BY NONEQUILIBRIUM MOLECULAR-DYNAMICS SIMULATIONS

In heme-containing proteins the heme group is usually non-covalently b ound in a pocket. Molecular dynamics (MD) simulations have been perfor med to estimate the burier height for heme-protein separation. In simu lations of myoglobin dissolved in water, a force has been applied to p ull the heme out of the binding pocket. With forces above 0.5 nN, the heme group is easily pulled out of the pocket in times of the order of tens of picoseconds. With weaker forces, heme release becomes too slo w to be monitored in an MD simulation covering a couple of hundred pic oseconds. These results are consistent with a free energy barrier to h eme release of about 100 kJ/mol. The results show that the main energe tic change that occurs during the release is a conversion of heme/prot ein Lennard-Jones energy into heme/water Lennard-Jones energy. The rel ease is essentially barrierless in energy indicating that the main put of the barrier is entropic. (C) 1998 Elsevier Science B.V. All rights reserved.