Force field optimization using dynamics and ensemble averaged data: vibrational spectra and relaxation in bound MbCO.

Force field parameters are ingredients for realistic atomistic simulations of gas- and condensed-phase systems. Here we discuss the effect of including averaged data from explicit MD simulations in optimizing potential energy functions. It is shown that vibrational frequencies (FeC and CO stretch and FeCO bend) and CO vibrational relaxation times ((v = 1) --> (v = 0) (T(10)) and (v = 2) --> (v = 1) (T(21))) in the active site of CO-bound myoglobin (MbCO) can be well represented with a single set of force field parameters. It is further demonstrated that parameters fitted in a subsystem of MbCO comprising the CO ligand, heme group and proximal histidine, are transferable to investigating the full protein and to providing quantitatively correct results. In particular, it is possible to calculate the CO and FeC stretch and the FeCO bending frequency to within approximately 5%; the relaxation time of the first vibrationally excited state including quantum corrections of T(10) approximately 25 ps is calculated close to the experimental value (17 ps), and the ratio T(10)/T(21) approximately 2 agrees favorably with experimental estimates. In contrast, following the more traditional approach of fitting frequencies from analyzing the Hessian matrix leads to a force field that captures frequencies correctly but not relaxation of vibrations.