Essential Dynamics sampling --------------------------- The results from Essential Dynamics (see sec. :ref:`covanal`) 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 :ref:`65 `, :ref:`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 :ref:`67 `. The procedure for essential dynamics sampling or flooding is as follows. First, the eigenvectors and eigenvalues need to be determined using covariance analysis (:ref:`gmx covar`) or normal-mode analysis (:ref:`gmx nmeig`). Then, this information is fed into :ref:`make_edi `, which has many options for selecting vectors and setting parameters, see ``gmx make_edi -h``. The generated :ref:`edi` input file is then passed to :ref:`mdrun `.