Hi Rob, thank you, your comments helped a lot.
From the Refmac5 paper I did not get the fact that d is set to d_current after each step. In that case you are right, jelly-body corresponds rather to DEN with gamma=1 than to gamma=0. And of course, a very important difference is, as you said, the fact that jelly-body is applied only to the second derivative. However, I would like to clarify this one point you made: For gamma=1 the DEN potential can follow anywhere, the entire conformational space is accessible and dij(t+1) depends only on Dij(t) and dij(t). The update formula is (again, for gamma=1): dij(t+1) = (1-kappa)*dij(t) + kappa * Dij(t+1) Dij(t) : distance between atom i and j and time t. dij_ref : distance between atom i and j in the reference structure. dij(t) : equilibrium distance of restraint between atom i and j at time t. The parameter kappa just defines how quickly dij(t) changes, i.e. kappa=1 sets dij(t+1)= Dij(t+1) at each time step. The parameter kappa is usually set to 0.1, which means the restraints slowly follow the atomic coordinates. But, again, the starting (or reference) model is completely forgotten and never used after the first iteration. This also means that the position of the minima of the target function are not changed by the DEN (gamma=1) restraints. It could just take longer to get there as the restraints need to be dragged along. For gamma<1, the situation is different, there are additional forces toward the reference (could be the starting) model, in which case dij(t+1) additionally depends on dij_ref. This also changes the position of the minima of the target function. It is therefore usually useful to run a final minimization without restraints to test whether the refinement reached a stable minimum of the target function. From the user perspective, I think the main difference is that DEN is designed to be used in simulated annealing MD refinement, whereas jelly-body is designed to be used in minimization (and cannot be used for MD refinement as there are no second derivatives). Cheers, Gunnar
