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I have encountered this issue while working with structures in PDB that are solved using Nuclear Magnetic Resonance (NMR). Which model should I choose among the 10 or 20 models? As a general rule of thumb, Model 1 is usually taken for further analysis and consideration. Is that rule universal for all NMR structures? Some studies on this topic makes it interesting to revisit.

On the outset, having an ensemble to work on is a goldmine of data. For more than one reason. Furnham et al [1] say that just like NMR, it would be great to have an ensemble created for X-ray structures too.

Such ensembles would be especially valuable in structural bioinformatics and rational drug design. For example, they would alter how local environments around residues are calculated and considered; this would have an impact on structural alignments, fold recognition, prediction of protein-protein interactions and docking.

ResearchBlogging.org
A minimized average structure is obtained by alinging the structures and finding the average position in Cartesian space for each atom across the ensemble. One of the measure of relatedness of the minimized average structure to the ensemble is the psi and phi torsion angles and its deviation from the ensemble. The other is the chi torsion angles. Analyzing the distribution of these angles it was found that there was no good correlation between an ensemble of structures and a single structure chosen to represent [2].

In considering NMR-derived structures it is vital to take into account the fact that parts of the structure usually on the surface of the protein are not well determined, either through inherent flexibility or lack of data. In general, for the protein core the result is comparable to a medium resolution (2.0 to 2.3 A) crystal structure [3].

In the words of Sutcliffe [2]

if an NMR structure is deposited as an ensemble of structures then it is advisable to study this ensemble as a whole rather than take select a single structure to represent it.

Specifically as described in his paper, one would want to find if the number of restraints derived experimentally is less (about 2 to 3) or more (about 15-20). This easily obtained by running PROCHECK-NMR [4] (http://www.ebi.ac.uk/thornton-srv/software/PROCHECK/nmr_manual/). The NMR restraints can be downloaded from PDB. Look for “NMR Restraints” under the “Download Files” tab.

Still, if one thinks for that particular protein of interest, an average structure would be the best way to go. Then one could use CARON [5] or CYANA [6]. The latter works better if you have access to experimental restraints from the authors.

I would love to hear about this from an NMRist, if that’s how they are called! ūüôā

References:

  1. Furnham, N., Blundell, T., DePristo, M., & Terwilliger, T. (2006). Is one solution good enough? Nature Structural & Molecular Biology, 13 (3), 184-185 DOI: 10.1038/nsmb0306-184
  2. Sutcliffe, M. (1993). Representing an ensemble of NMR-derived protein structures by a single structure Protein Science, 2 (6), 936-944 DOI: 10.1002/pro.5560020607
  3. MacArthur, M., & Thornton, J. (1993). Conformational analysis of protein structures derived from NMR data Proteins: Structure, Function, and Genetics, 17 (3), 232-251 DOI: 10.1002/prot.340170303
  4. Laskowski, R., Rullmann, J., MacArthur, M., Kaptein, R., & Thornton, J. (1996). AQUA and PROCHECK-NMR: Programs for checking the quality of protein structures solved by NMR Journal of Biomolecular NMR, 8 (4) DOI: 10.1007/BF00228148
  5. Sikic K, & Carugo O (2009). CARON–average RMSD of NMR structure ensembles. Bioinformation, 4 (3), 132-3 PMID: 20198187
  6. Gottstein, D., Kirchner, D., & G√ľntert, P. (2012). Simultaneous single-structure and bundle representation of protein NMR structures in torsion angle space Journal of Biomolecular NMR, 52 (4), 351-364 DOI: 10.1007/s10858-012-9615-8

This animated GIF is an awesome teaching tool for explaining glycolysis. Click on the image to see the animation

Just Science

animated glycolysis gif, animated biochemistry gif

Hexokinase, Phosphoglucose Isomerase, Phosphofructokinase (PFK), Fructose 1,6-bisphosphate aldolase, Triose Phosphate Isomerase, Glyceraldehyde-3-Phosphate Dehydrogenase, Phosphoglycerate Kinase, Phosphoglycerate Mutase, Enolase, and Pyruvate Kinase.

The protein structure at the top below the plasma membrane (blue) is the cytoplasmic portion of Mannose PTS permease that transports glucose into the cell. In the animation, glucose enters the cell and is converted down the glycolytic enzyme path into the correct product structures until ultimately 2 molecules of pyruvate are produced for processing within another cellular pathway.

Related articles

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So, here is an imaginary situation. You have a deadline to achieve and have minimal internet to reach the goal. Few hours before the deadline, your PI asks if you can send him a movie of the protein of interest in PyMOL. He specifies that the movie show the protein rotating, the active site and the ligand bound with it in surface representation, ligands as ball-and-stick, etc. He has a grant review presentation tomorrow and needs it asap.

You finish the movie and realize that to make a good impression one would need a high quality movie and that is going to eat up your internet time in uploading and you may end up not achieving both (Yours and your PI’s)¬†goals.

Ta da! That’s where you need POLYVIEW-3D.

  • It is quick and easy to use
  • Easy interface with no complex manuvering required.
  • Best part are the animated gifs, that are easy to send via email.
  • You can set an orientation using the Jmol java applet.
  • You can choose either RasMol or PyMOL rendering
  • From tiny images (50×50 pixels for lab webpages) to large sized pictures (1000×1000 pixels for presentations)
  • PNG and TIF format for static images. Animated ones are (of course) in Gif format.

Some of the images I made using this web-server

1ece

1362694869549_hl

One chain in surface colored w.r.t hydrophilicity and another in Cartoon colored w.r.t secondary structure, with halo lighting

1362694869549

One chain in surface colored w.r.t hydrophilicity and another in Cartoon colored w.r.t secondary structure, without halo lighting

13626952246586

Chain A showing the active site, with ligand bound. The residues interacting with ligand are colored blue. Only one ligand, the other one is from chain B.

13626954442831

Same as above, with animation.

I think this cool, give it a try!

References:

ResearchBlogging.orgPorollo, A., & Meller, J. (2007). Versatile annotation and publication quality visualization of protein complexes using POLYVIEW-3D BMC Bioinformatics, 8 (1) DOI: 10.1186/1471-2105-8-316