Molecular Dynamics Flexible Fitting
The molecular dynamics flexible fitting (MDFF) method can be used to flexibly fit atomic structures into density maps. The method consists of adding external forces proportional to the gradient of the density map into a molecular dynamics (MD) simulation of the atomic structure.xMDFF for X-ray Crystallography
Recently, we have developed a new MDFF-based approach, xMDFF, for determining structures from such low-resolution crystallographic data. xMDFF employs a real-space refinement scheme that flexibly fits atomic models into an iteratively updating electron density map. It addresses significant large-scale deformations of the initial model to fit the low-resolution density.
Use the menu above to navigate the MDFF website. For examples of MDFF applications, visit the websites on Mechanisms of Protein Synthesis by the Ribosome, Dynamics of Protein Translocation, Molecular Dynamics of Viruses, and Intrinsic Curvature Properties of Photosynthetic Proteins in Chromatophore.
Recent News and Announcements: VMD 1.9.2 Released (December 2014)
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VMD 1.9.2 contains several updates for the Molecular Dynamics Flexible Fitting (MDFF) Method. The mdff plugin contains new options for setting up MDFF simulations with implicit solvent and the new MDFF method for low-resolution x-ray crystallography (xMDFF, recently detailed in this article). Complete details for setting up xMDFF simulations with this plugin can be found in the MDFF tutorial. Additionally, a new graphical user interface for the mdff plugin is now available in the Modeling section of the Extensions menu. This interface allows for easier setup of MDFF and xMDFF simulations, as well as running, connecting to, and analyzing interactive MD simulations. VMD 1.9.2 also contains new multi-core CPU and GPU-accelerated analysis capabilities for MDFF, as described in a recent article. The mdffi cc command can be used to quickly compute the cross correlation of a structure to a target density map much faster than previous methods. This speedup allows for the analysis of very large structures (millions of atoms) and very long (microsecond range) trajectories, and at a much finer level of detail than was previously feasible. The Timeline plugin uses this new fast cross correlation method to visually present the results of the analysis, making it easier than ever to determine the quality of fit for a MDFF simulation and to quickly identify poorly fitting regions of a structure that require further simulation. More information about other latest features of VMD version 1.9.2 can be found on the release page.
Spotlight: xMDFF Enhances X-ray Structures (Aug 2014)
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For many, the word 'X-ray' conjures up the images of white bones on black backgrounds hanging on the wall of a doctor's office. However, X-rays have played another important role for the past 100 years through their use in the determination of chemical structures at atomic level detail, starting with the first ever structure of table salt in 1924. Since then, the diffraction properties of X-rays, when shone on a crystal, have been used to solve increasingly large and complex structures including those of biological macromolecules found inside living cells. X-ray crystallography has become the most versatile and dominant technique for determining atomic structures of biomolecules, but despite its strengths, X-ray crystallography struggles in the case of large or flexible structures as well as in the case of membrane proteins, either of which diffract only at low resolutions. Because solving structures from low-resolution data is a difficult, time-consuming process, such data sets are often discarded. To face the challenges posed by low-resolution, new methods, such as xMDFF (Molecular Dynamics Flexible Fitting for X-ray Crystallography) described here, are being developed. xMDFF extends the popular MDFF software originally created for determining atomic-resolution structures from cryo-electron microscopy density maps (see the previous highlights Seeing Molecular Machines in Action, Open Sesame, Placing New Proteins, and Elusive HIV-1 Capsid). xMDFF provides a relatively easy solution to the difficult process of refining structures from low-resolution data. The method has been successfully applied to experimental data as described in a recent article where xMDFF refinement is explained in detail and its use is demonstrated. Together with electrophysiology experiments, xMDFF was also used to validate the first all-atom structure of the voltage sensing protein Ci-VSP, as also recently reported. More on our MDFF website.