Flex-EM includes a rigid fitting stage followed by a refinement stage. Rigid fitting can be performed with Mod-EM or any other rigid fitting methods. The refinement stage starts with the components rigidly fitted in the approximate positions in the map. Two methods are available: conjugate gradients minimization (CG) and simulated annealing molecular dynamics (MD).
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M. Topf, K. Lasker, B. Webb, H. Wolfson, W. Chiu, A. Sali.
Protein Structure Fitting and Refinement Guided by Cryo-EM Density
Structure 16, 295-307, 2008