Molecular dynamics simulations of CN- dynamics and spectroscopy in myoglobin.

The vibrational dynamics of the cyanide anion and the heme group in MbCN (CN complexed to Myoglobin) are investigated using molecular dynamics simulations. A previously calculated quantum-chemical heme-ligand potential-energy surface together with a three-center charge model for the iron-ligand center that captures both polarization and ligand-to-metal charge transfer allows for a detailed description of the interactions around the active site. It is found that the CN binding orientation (Fe--CN or Fe--NC) to the heme affects the stretching frequency of the ligand, with a 25 cm-1 difference in the fundamental wavenumber between the two orientations as well as a change in bond length. The charge model also captures such crucial interactions as the possible hydrogen bond between the ligand and the His64 residue. This interaction is weakened when the ligand binds in the Fe--NC conformation but is also sensitive to the protonation state of His64. The structural changes around the active site, the observation of water penetration for the Fe--NC conformation, the computed IR spectrum, and the energetics suggest that the Fe--CN conformation with Hisepsilon64 is the most likely one. The water accessibility of the active site is also found to be related to the protonation state of His64. The presence of water in the active site could also affect the IR band of the C--N stretch mode. Thus, IR spectroscopy of the C--N stretch is a potentially useful reporter of ligand isomers and active-site structure.