Advances in the molecular dynamics flexible fitting method for cryo-EM modeling.

Molecular Dynamics Flexible Fitting (MDFF) is an established technique for fitting all-atom structures of molecules into corresponding cryo-electron microscopy (cryo-EM) densities. The practical application of MDFF is simple but requires a user to be aware of and take measures against a variety of possible challenges presented by each individual case. Some of these challenges arise from the complexity of a molecular structure or the limited quality of available structural models and densities to be interpreted, while others stem from the intricacies of MDFF itself. The current article serves as an overview of the strategies that have been developed since MDFF's inception to overcome common challenges and successfully perform MDFF simulations.