[Chimera-users] How to check flexibility of a protein

[Elaine Meng]

Hi Shazia,
Chimera does not predict flexibility of a protein.  However, the experimental data may have some clues.

If the structure is from crystallography, the B-factor values may be useful.  You can show B-factor with colors, radii, or “worm” fatness using the Render by Attribute tool, or with colors using the command “rangecolor,” for example:

rangecolor bfactor min blue mid red max yellow

<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/render/render.html#render>
<http://www.rbvi.ucsf.edu/chimera/docs/UsersGuide/midas/rangecolor.html>

If the structure is from NMR or a MD simulation and you have an ensemble (multiple conformations) rather than just one set of coordinates, you can superimpose the different conformations and see which parts are more variable spatially. In addition or as an alternative, the RMSD at each position can be shown with color or worm fatness, similar to the B-factor.  For example, see this previous post:
<http://plato.cgl.ucsf.edu/pipermail/chimera-users/2014-March/009710.html>

Chimera also does not predict flexibility changes from mutation.  You can make the mutation computationally, but It will only change the sidechain and not move anything else.  You can analyze how H-bonds and clashes (bad contacts) may change resulting from the mutation, but it is only a first-order estimate.   You would still have to use your scientific intuition as to how it might affect the protein's structure or flexibility.

Computational mutation can be done with the Rotamers tool (in menu under Tools... Structure Editing) or the "swapaa" command.  There is an example of using the Rotamers tool in the "Structure Analysis and Comparison" tutorial:
<http://www.rbvi.ucsf.edu/chimera/docs/UsersGuide/tutorials/squalene.html>
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/rotamers/rotamers.html>
<http://www.rbvi.ucsf.edu/chimera/docs/UsersGuide/midas/swapaa.html>

You can do some energy-minimization, but it has very limited ability to change the structure.
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/minimize/minimize.html>

In the new release (1.11 available from our download page), there is also a Molecular Dynamics tool, but keep in mind that a thorough investigation of flexibility would require very long simulations including solvent.
<http://www.rbvi.ucsf.edu/chimera/docs/ContributedSoftware/md/md.html>

I hope this helps,
Elaine
----------
Elaine C. Meng, Ph.D. 
UCSF Computer Graphics Lab (Chimera team) and Babbitt Lab
Department of Pharmaceutical Chemistry
University of California, San Francisco

> On Jun 14, 2016, at 12:04 AM, shazia sabir <s.syed005 at gmail.com> wrote:
> 
> Can we check flexibility of a protein in chimera? Can we see if protein is affected after a mutation of only single amino acid? Are there some parameters that shows protein become more rigid or flexible after mutation? 
>   Regards, 
>   Shazia.