Protein Pirouettes: Part 2


Welcome to our Protein Pirouettes series! This series is designed to teach you about the wonderful world of proteins, so that you too can learn to dance like a protein. If you haven’t read our introduction- check out the first part of the series here. You can also watch this great video here– for expert level dancing on the smallest possible scale. For more information about the author, check out our about us page.

Hello readers! Cooper here! Welcome back to our Protein Pirouettes series. In the last article, I talked a lot about where proteins come from, why they need to fold, and touched on the elaborate dance of protein folding that proteins must perform to function. In this article, we’ll dive deeper into this process, and explore what happens when it goes horribly wrong. 

When you’re stuck in a rut, just keep dancing.

As proteins twist and turn, they take on different shapes that we call conformations. In search of a functional, highly organized, low entropy shape, proteins sometimes get stuck into non-native conformations (intermediately folded states, or simply called intermediates).2These chaotic, entropy laden states are intermediates on the pathway towards fulfillment of the protein’s purpose. Oh, woe is the protein! But do the little dancers give up? Of course not—they do what they always do. They dance

Protein Chain Diagram
Simplified protein folding funnel, showing a handsomely drawn protein perform the Cha Cha slide. Two hops this time!


The protein vibrates with wanton abandon, strands of amino acids bumping into each another recklessly and randomly, trying out new moves. It doesn’t give up. Eventually, something just seems to feel right, the protein settles into its groove and becomes more stable, escaping the rut and dancing towards its goal. When faced with a hurdle in life, consider meeting the challenge like a protein: just keep dancing.

Friends don’t let friends dance alone.

Remember the chaperones at your high school prom? Proteins don’t always get to dance without chaperones either. Sometimes, to dance their way to the next conformation, proteins enlist the help of a chaperone.3Chaperones are protein themselves, and when they see a fellow protein dancing, they get up and dance along with them! Cells are like busy night clubs, and it’s hard to dance when there are innumerable other proteins dancing all around you! Just like our high school prom chaperones, protein chaperones facilitate the party so that nothing too-crazy happens. After all, sometimes dancing doesn’t turn out like it should. 

If you’re an amyloid, you’re going to have a bad time.

Go home amyloid, you’re drunk.

Without the safe watch of a chaperone, proteins may accidentally take on a misfolded conformation that is particularly terrible. These misfolded proteins are like that guy at prom that drinks a little bittoo much of the booze he stole from his parents, and ends up vomiting all over the hardwood dance floor of the gym. Don’t be that guy. Proteins don’t want to be that guy either, and, in the world of proteins, that guy’s name is amyloid.3Amyloids form when misfolded proteins get squished together, and they’re dangerous to your health. For example, plaques of amyloid beta proteins are implicated in the development of Alzheimer’s disease.6So, take a tip from proteins: dance responsibly. 



  1. Video clip of a protein folding simulation.1
  2. Protein folding funnel drawn in Microsoft Paint. The width of the funnel represent entropy, with decreasing entropy as the funnel narrows. The height of the funnel represents Gibbs free energy, with energy decreasing from top to bottom.2
  3. Adapted, surface structure of a 42-residue beta-amyloid fibril (2MXU) visualized in NGL.4-5


  1. Theoretical and Computational Biophysics Group at the NIH Center for Macromolecular Modeling and Bioinformatics. Folding of a Three-helix Bundle Protein. Online video clip. YouTube. 2013. Retrieved from
  2. Wolynes PG, Onuchic JN, Thirumalai D. Navigating the Folding Routes. Science. 1995;267(5204):1619.
  3. Dwevedi A. Protein Folding: Examining the Challenges from Synthesis to Folded Form. SpringerBriefs in Biochemistry and Molecular Biology. 2015. ISBN 978-3-319-12592-3. 
  4. AS Rose, AR Bradley, Y Valasatava, JM Duarte, A Prlić and PW Rose. Web-based molecular graphics for large complexes. ACM Proceedings of the 21st International Conference on Web3D Technology (Web3D ’16): 185-186, 2016. doi:10.1145/2945292.2945324.
  5. AS Rose and PW Hildebrand. NGL Viewer: a web application for molecular visualization. Nucl Acids Res (1 July 2015) 43 (W1): W576-W579 first published online April 29, 2015. doi:10.1093/nar/gkv402.
  6. Aisen PS, Cummings J, Jack Jr. CR, et al. On the path to 2025: understanding the Alzheimer’s disease continuum. Alzheimers Res Ther. 2017;9:60. doi:10.1186/s13195-017-0283-5.