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.
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: Structure of HIV (May 2013)
The capsid of the human immunodeficiency virus type 1 (HIV-1), the major cause of AIDS, has recently had its full atomic structure determined. This discovery was made in part through the use of MDFF and marks the largest structure ever determined utilizing MDFF, at over 3 million atoms. This feat was made possible due to the performance and scalability of NAMD which MDFF is built into. This integration with NAMD allows MDFF to be run on a wide variety of platforms, including large supercomputers such as BlueWaters which was used for simulating the HIV capsid. In addition, due to the MD based nature of MDFF, the capsid structure could be immediately used for the additional simulations which took place after the initial fitting. More information is available in this highlight.
Spotlight: Elusive HIV-1 Capsid (Jun 2013)
Human immunodeficiency virus type 1 (HIV-1) is the major cause of AIDS, for which treatments need to be developed continuously as the virus becomes quickly resistant to new drugs. When the virus infects a human cell it releases into the cell its capsid, a closed, stable container protecting the viral genetic material. However, interaction with the cell triggers at some point an instability of the capsid, leading to a well timed release of the genetic material that merges then with the cell's genes and begins to control the cell. The dual role of the capsid, to be functionally both stable and unstable, makes it in principle an ideal target for antiviral drugs and, in fact, treatments of other viral infections successfully target the respective capsids. The size of the HIV-1 capsid (about 1,300 proteins), and its irregular shape had prevented so far the resolution of a full capsid atomic-level structure. However, in a tour de force effort, groups of experimental and computational scientists have now resolved the capsid's chemical structure (deposited to the protein data bank under the accession codes 3J3Q and 3J3Y). As reported recently (see also journal cover), the researchers combined NMR structure analysis, electron microscopy and data-guided molecular dynamics simulations utilizing VMD to prepare and analyze simulations performed using NAMD on one of the most powerful computers worldwide, Blue Waters, to obtain and characterize the HIV-1 capsid. The discovery can guide now the design of novel drugs for enhanced antiviral therapy. More information is available on our virus website, in video, and in a press release.