Illustration of DEN for an example with two atoms. The elastic network potential is represented by a spring (orange) between two atoms (black balls) separated by a distance of

*d*_{ij} (

*n*) for the atom pair (

*i,j*) at sampling step

*n*. The density map contours are represented by blue iso-contours. The energy terms involved are depicted in the diagrams on the right. The current equilibrium distance

of the DEN potential,

, can change at each sampling step

*n*. The blue curve shows the rugged pseudo-energy

*E*_{ρ} (see

*Experimental Procedures*), which is minimal for the best fit of the model density to the target density map. At the start of the sampling simulation process, the distance of the atoms

in the starting model is at the minimum of the DEN potential,

(dashed orange line). As the elastic network deforms by changing the equilibrium distance

to

, the DEN potential,

, also changes (solid orange line). (A) Three steps (n, n+1, and n+2) of a sampling simulation are shown for the parameter γ = 0.5. In the starting model, the two atoms are close to each other. During the sampling simulation the atoms are pulled into higher density regions. The DEN potential adapts to this force up to an extent that is controlled by γ (see in

*Experimental Procedures*). (B) shows the final converged states of three different sampling simulations for different γ-values (0.1, 0.5, 0.9). The larger the value of γ, the more the DEN is able to adapt to the forces imposed by the density map.

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