Md Simulations of Carbonmonoxy Myoglobin and Calculations of Heme Cd

i The Soret circular dichroism (CD) spectrum of carbonmonoxy myoglobin dtifers strikingly for the two heme isomers: Aqzl =+90 M-’cm-’ for isomer A, AQ21 = -7 M-’cm-’ for isomer B (Aojula et al., BiochemJ. 250, 853(1988)). This observation implies significant differences in the protein conformation andlor distortions of the heme from planarity between the two isomers. Molecular dynamics simulations of the two isomers have been performed, using both neutron diffraction (ND) and NMR structures for stwting geometries. The geometry for isomer B was generated from the isomer A geometry by rotation of the heme by 180° about the a-y methine carbon axis. Four ND-based trajectories for isomer A, each of 600 ps duration, gave average CD spectra that reproduced the strong positive Soret CD inferred for isomer from experiment. Four such trajectories for isomer B gave results similar to those for isomer A, and therefore disagreed with the weak negative Soret CD band inferred from experiment for isomer B. The two NMR-based hajectories for each isomer gave poor agreement with experiment. We attribute the failure of the calculations for isomer B to a poor starting structure for this isomer, and we are conducting further studies to overcome this problem. In the successful calculations for isomer A, heme-aromatic side chain coupling accounts for 1