We are continually adding new features to QwikMD (and expanding the spotlight to highlight more of the existing features of QwikMD) so come back and visit often.


While waste recycling in daily life has become popular only recently, living cells have been recycling their protein content since the very beginning. Recycling of unneeded protein molecules in cells is performed by a molecular machine called the proteasome, which cuts these proteins into smaller pieces for reuse as building blocks for new proteins. Proteins that need to be recycled are labeled by tags made of poly-ubiquitin protein chains. The proteasome machine recognizes and binds to these tags, pulls the tagged protein close, then unwinds it, and finally cuts it into pieces. Despite its substantial role in the cell's life cycle, the proteasome's atomic structure and function still remain elusive. In our recent study, we obtained an atomic structure of the human 26S proteasome by combining computational modeling techniques, through molecular dynamics flexible fitting (MDFF) of the cryo-electron microscopy (cryo-EM) data. The features observed in the resulting structure are important for coordinating the proteasomal subunits during protein recycling. One of the key advances is that for the first time the nucleotides bound to the ATPase motor of the proteasome are resolved. The atomic resolution of the structure permits to perform molecular dynamics simulations to investigate the detailed proteasomal function, in particular the protein unwinding process of the ATPase motor. Furthermore, our obtained structure will serve as a starting point for structure-guided drug discovery, developing the proteasome as a crucial drug target. The atomic models are deposited in the protein data bank (PDB) with the PDB IDs 5L4G and 5L4K and the 3.9 Å resolution cryo-EM density is deposited in the electron microscopy data bank EMD-4002. More information about our proteasome projects is available on our proteasome website. Easy access to our modeling techniques is provided through QwikMD, which was employed here for the first time.
Proteasome


Everything that living things do can be understood in terms of jigglings and wigglings of atoms. Richard Feynman's remark in the early 1960's summarizes what is today widely accepted, namely, that molecular processes can be described by the dynamics of biological molecules, therefore connecting protein dynamics to biological function. Molecular dynamics (MD) is by far the best tool to investigate jigglings and wigglings of biological systems. Advances in both software and hardware have spread the use of MD, however the steepness of the learning curve of the methodology of MD remains high. To assist new users in overcoming the initial barrier to use MD software, and to help the more advanced users to speed up tedious steps, a new software, namely QwikMD, was presented. By incorporating an easy-to-use point-and-click user interface that connects the widely used molecular graphics program VMD with the powerful MD program NAMD, QwikMD allows its users to prepare both basic and advanced MD simulations in just a few minutes. At the same time, QwikMD keeps track of every step performed during the preparation of the simulation, allowing easy reproducibility and shareability of protocols. More information about QwikMD, as well as introductory tutorials are available on our QwikMD webpage. QwikMD is available in VMD.1.9.3 or later versions.
QwikMD


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