CHARMM-GUI MDFF/xMDFF Utilizer for Molecular Dynamics Flexible Fitting Simulations in Various Environments.

X-ray crystallography and cryo-electron microscopy are two popular methods for the structure determination of biological molecules. Atomic structures are derived through the fitting and refinement of an initial model into electron density maps constructed by both experiments. Two computational approaches, MDFF and xMDFF, have been developed to facilitate this process by integrating the experimental data with molecular dynamics simulation. However, the setup of an MDFF/xMDFF simulation requires knowledge of both experimental and computational methods, which is not straightforward for nonexpert users. In addition, sometimes it is desirable to include realistic environments, such as explicit solvent and lipid bilayers during the simulation, which poses another challenge even for expert users. To alleviate these difficulties, we have developed MDFF/xMDFF Utilizer in CHARMM-GUI that helps users to set up an MDFF/xMDFF simulation. The capability of MDFF/xMDFF Utilizer is greatly enhanced by integration with other CHARMM-GUI modules, including protein structure manipulation, a diverse set of lipid types, and all-atom CHARMM and coarse-grained PACE force fields. With this integration, various simulation environments are available for MDFF Utilizer (vacuum, implicit/explicit solvent, and bilayers) and xMDFF Utilizer (vacuum and solution). In this work, three examples are shown to demonstrate the usage of MDFF/xMDFF Utilizer.