Hinge regions are typically in between domains in a protein and allow flexibility. i.e. They allow the domains to move relative to one another. Some enzymes use hinge regions to allow the surrounding domains to "clamp down" on their substrates.

In terms of what kinds of residues can be found in hinge regions, the answer is all kinds. I'm not aware of a systematic survey of known hinge regions that identifies specific residue types (such a survey may exist, but I'm haven't seen it).

It would help if you could clarify your question. Are you saying you have a protein that you think may have a hinge region and you want to identify where it is in the structure? Is the structure known?

Hello Manan,

You might find these publications useful:

F. Ding, K. C. Prutzman, S. L. Campbell, and N. V. Dokholyan, "Topological determinants of protein domain swapping", Structure, 14: 5-14 (2006).

Hirose et al. Prediction of protein motions from amino acid sequence and its application to protein-protein interaction. BMC Structural Biology 2010, 10:20.

Andrei

Hello Trevor, thanks for the answer. Well I do have a protein and i believe a particular region of it may act as a putative hinge. The structure of the protein is known. However, i do not have or know of a way to prove whether this region is or could be a potential hinge

Hi Andrei, thank you for the the references

Hello manan, well as the hinge region is responsible for the flexibility, try some site directed mutations in the region and try understanding dynamics or loop movement through florescent probes.

Vandana is right! However do you have any reacting Cys in your protein;if no then the easiest way will be two generate a double cys mutant with 1 in each domain and probe dynamics of loop movement via fret betwwen two flurophores at those 2 cys....makes sense?

To Vandana and Aritra, thank you fro the suggestions, however, my work is in silico and not in vitro or in vivo...

Then watever you do you cannot tell for certain!!

Dear Manan,

I had a quick look at all your questions on Research Gate. Your work is mostly focused on modeling and bioinformatics. In reference to this there are many web services that deal with the hinge problems. As far as I know there is no systematic study on the issue because in order to do that, there must be a certain view of proteins assumed. So, most of the software is focused on researching data bases, such as PDB, and drawing the statistical conclusions.

You might greatly benefit from reading my responses I posted to other questions asked on RG that basically summarize my views on the subject. These are:

https://www.researchgate.net/post/What_percentage_of_residues_do_you_typically_observe_in_disallowed_regions_of_the_Ramachandran_plot

https://www.researchgate.net/post/protein_folding_and_stability

These posts summarize my views on protein structure as a composite of solid and liquid state contributions to the protein structure. The main findings are published in PNAS 106(2009)10505.

You might also want to read my recent paper

FEBS letters. 05/2012; 586(12):1675-7.

in which I cite several sources concerning the hinges.

This is a great unexplored area that needs work. The entire field of structurally unfolded (disordered) proteins was born out of questions like this. If you want to chat more please contact me directly.

However, after having said all of the above I have to agree with the majority of other participants that only good experimental work (mutagenesis, fluorescence, or NMR) would address properly the details of your question and provide answers.

You may want to try a normal mode analysis to see if it predicts large scale conformational changes involving your hinge region. There are several servers on the web for doing this, e.g. Webnma (http://apps.cbu.uib.no/webnma/home).

Hi Trevor thanks for the suggestion and the link to the server

Also i would like to know whether results obtained from predictions using ANM web server (http://ignmtest.ccbb.pitt.edu/cgi-bin/anm/anm1.cgi) be considered reliable

That I can't answer - it's not my field of expertise. You'll probably have to look through the literature to find the answer to that.

Hi Manan,

Hinge regions are stretches of a protein that can be involved in the propagation of conformational changes e.g. from the active site to the rest of the protein structure, including other subunits. They could be small loops in between secondary structures. It is possible that a large conformational change occurs on a protein without any change in the secondary structure (assessed by circular dichroism), and it is believed that hinge regions play a significant role in the process. This can be done in different ways such as bending or rotation and in order for this to happen, hinge regions must be flexible.

Answering your question, I wouldn´t expect that a region containing residues with a bulky side chain like a proline to be much flexible, because there would be steric hindrance for movement.

Some ways to test whether a region is or not a hinge region could be to do some point mutations to decrease the flexibility of a region and measure how that affects a known conformational change.

Also, if you know that the secondary structural elements are not likely involved in a conformational change, you could try to fix these elements and run a MD simulation having only the possible hinge regions flexible and test what happens when a substrate binds, for example.

Thank you Raquel, well i did try inducing point mutations and look at the bending... there was a very subtle difference so not sure if it would considered significant . In addition im trying to attempt docking another protein and check the binding energies

Hinge regions typically link multi-domain proteins, for example alanine racemase. If you have a starting structure or good homology model, you can generate quite informative in silico analysis of your hinge domains. Follow Raquel Cravalho's suggestions above. To measure the variations in the hinge domain using freeware you can use the CCP4 suite specifically a program "Dyndom". Also you can find a list of freeware that can help you in analyzing hinge domains in your "predicted" structures at this link http://bip.weizmann.ac.il/toolbox/structure/tertiary.htm

Best of luck.