MOLECULAR-DYNAMICS STUDY OF THE PHOTODISSOCIATION OF CARBON-MONOXIDE FROM MYOGLOBIN - LIGAND DYNAMICS IN THE 1ST 10 PS

Molecular dynamics simulations are used to study the dynamics of carbon monoxide following its photodissociation from the protein myoglobin. The stochastic boundary approximation is employed for the heme pocket in the presence of solvent. A new three-site model is used for the carbon monoxide that represents its quadrupole moment and includes anharmonic effects in its internal vibrations. The role of the protonation state of the distal histidine and its effect on the dynamics and conformation of the unbound ligand are determined. Analysis of the center-of-mass, rotational and vibrational dynamics of the ligand agrees well with the experimental data of Anfinrud, Han and Hochstrasser [Proc. Natl. Acad. Sci. USA 86 (1989) 8387]. The study seeks to interpret experimental data on the presence of binding sites in the heme pocket (corresponding to both red and blue shifts in the ligand vibrational frequency) which are reached by the ligand soon after dissociation, remain stable for upwards of 1 ns, and whose relative populations are strongly dependent on pH. The possibility that hydrogen bonding of the ligand to the distal histidine may account for ligand vibrational frequency shifts observed experimentally is explored through ab initio frequency calculations. Although the distal histidine clearly is involved, other interactions appear to be required to explain the observed red shifts.