Molecular dynamics simulation anharmonic contributions

An additional factor to consider is the magnitude of the anharmonic contribution to the entropy of proteins. Analyses of molecular dynamics simulations have demonstrated that the major anharmonic contributions can be ascribed to multiple conformations for individual atoms.195 In BPTI and lysozyme, an estimate of the change in entropy due to these effects (e.g., 89 atoms in lysozyme have multiple wells) yields a correction of less than 2% for the classical entropy. Thus multiple conformations appear not to be important for the residual entropy at ordinary temperatures.389 However, near absolute zero (1 to 2 K) there are data that suggest that several minima ( tunneling states ) contributes significantly to the entropy.390... 

The advantage of this method is that it can be used for more complicated systems, where explicit calculation of the full dynamical matrix would be extremely expensive. Furthermore, we can calculate the temperature dependence of the phonon spectrum by simply performing molecular dynamics simulations at different temperatures. The temperature dependence of the phonon spectrum is due to anharmonic effects, i.e., at larger displacements when terms higher than second order contribute to the potential energy in Eq. 5.4. 

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