Essential Dynamics sampling

The results from Essential Dynamics (see sec. Covariance analysis) of a protein can be used to guide MD simulations. The idea is that from an initial MD simulation (or from other sources) a definition of the collective fluctuations with largest amplitude is obtained. The position along one or more of these collective modes can be constrained in a (second) MD simulation in a number of ways for several purposes. For example, the position along a certain mode may be kept fixed to monitor the average force (free-energy gradient) on that coordinate in that position. Another application is to enhance sampling efficiency with respect to usual MD 65, 66. In this case, the system is encouraged to sample its available configuration space more systematically than in a diffusion-like path that proteins usually take.

Another possibility to enhance sampling is flooding. Here a flooding potential is added to certain (collective) degrees of freedom to expel the system out of a region of phase space 67.

The procedure for essential dynamics sampling or flooding is as follows. First, the eigenvectors and eigenvalues need to be determined using covariance analysis (gmx covar) or normal-mode analysis (gmx nmeig). Then, this information is fed into make_edi, which has many options for selecting vectors and setting parameters, see gmx make_edi -h. The generated edi input file is then passed to mdrun.