Superoxide Dismutase Partially unfolding

If you don't want to be bored with (or confused by) technical details, skip to the last paragraph.

This is Human Cu, Zn Superoxide Dismutase partially unfolding. The simulation is 20ns long in explicit solvent. The starting structure was a Cu-deficient, bridge-reduced NMR structure.

The Zn was removed, 15,094 TIP3P water molecules were added. NAMD was used to minimize the system for 10,000 steps, then heated slowly (over 1.25ns) to 300K in the canonical ensemble. The temperature was incremented by 0.001K every 4fs. Equilibration was for 600ps in the isobaric-isothermal ensemble. The system was then simulated for 20ns with 2fs time steps at 300K, also in the isobaric-isothermal ensemble. All simulations were performed with periodic boundary conditions.

The simulations were performed on a Linux Beowulf class cluster, using NAMD 2.6. Each node, running fedora core 2, has 2 AMD Opteron 244 processors and 4GB of ECC ram. 10 Processors were used. The simulation took 3 weeks.

To make this video, the TIP3P water molecules were removed, subunits separated. Translations and rotations were removed by fitting each structure to one reference structure using a least-squares fit of the beta-barrel alpha carbons.

The video was generated by taking screen captures of the VMD trajectory window. Every 10th frame of the trajectory (20,000 total) was used, with smoothing set to 20 (each frame is an average of the 20 frames preceding it). The images were then converted into a video using a freeware video editing program for windows called VirtualDub. Not one piece of software used to make this video cost a dime (NAMD, VMD, and VirtualDub are all free).

What you are looking for is the movement of the cyan/white/magenta loops on the left side of the window. Note how they fold from a hinge at the edge of the barrel (gray). This colored section of the protein is important not only for its function, but also its stability. The unfolding you see can lead to aggregation and the resulting toxicity has been implicated in Familial Amyotrophic Lateral Sclerosis (Lou Gehrig's Disease). Much is still not understood about this protein. It's fascinating.

Category:

Science & Technology

Tags:

• protein
• folding
• unfolding
• superoxide
• dismutase
• Lou
• Gehrig's
• Disease
• molecular
• dynamics
• biophysics

[q0L0b]

very nice.