Open Letters

More thoughts on folding and form

Maurizio Brunori Arianna Brunori
By Maurizio Brunori and Arianna Brunori
Oct. 28, 2020

We were pleased to read Sudha Neelam’s pleasant and stimulating essay, “The art of paper folding and the science of protein folding,”in ASBMB Today.

Daniel Álvasd/ Unsplash

Outlining the similarity between an origami and a folded protein is quite popular, since in both the form combines beauty and functional relevance. In both cases, the mechanism of folding to achieve the final state is complex. This similarity has been taken further to highlight that a misfolded origami mimics in some way a misfolded protein seen at the onset of neurodegenerative diseases that develop via irreversible population of an amyloid state by extensive misaggregation.

Jawahar Swaminathan/
European Bioinformatics Institute

We should, however, recall one difference between folding a paper sheet and a polypeptide chain, a difference that is of fundamental significance.

The complex course of action to fold a paper sheet to produce origami of a chosen shape demands that precise information be injected in the procedure by an operator (in this specific case, Nihkil, the son of the writer Sudha Neelam). The order of guided steps is essential to overcome the loss of entropy coupled to the creation of an ordered object, such as a classical origami sculpture.

Jörg Bittner Unna/Wikimedia Commons

In the case of folding a complex 3D structurestarting from one disordered polypeptide, the information guiding the series of events/chemical steps leading to the globular protein is imprinted within the amino acid sequence. The primary structure itself is also the code carrying the instructions on how to fold in water and thereby the information to overcome the huge, unfavorable entropy loss.

In water, the amino acid sequence of a protein conforms beautifully to Aristotle’s definition of substance, the intimate ensemble of matter and form (in Greek: “synolon”), insofar as the amino acid sequence contains in itself the reason for becoming what it is (in Latin: “substantia causa sui”). In this respect, we can compare the amino acid sequence to the marble block as seen by Michelangelo Buonarroti. In Michelangelo’s view, the artist need only bring into actuality the form that already lies in the marble block by chiseling away the superfluous material.

Likewise, as shown by Nobel laureate Christian Anfinsen, the amino acid sequence embeds from the beginning the properties that will characterize the protein in the final functionally competent native state, needing only water to pass from potentiality into actuality.


Maurizio Brunori
Maurizio Brunori

Maurizio Brunori is emeritus president of the National Academy of the Lincei and professor emeritus at the Sapienza University of Rome.

Arianna Brunori
Arianna Brunori

Arianna Brunori is a Ph.D. student in medieval philosophy at the Scuola Normale Superiore di Pisa.

Related articles

Become the protein
Laurel Oldach
Tour de flippase
Todd R. Graham
From the journals: MCP
Shravanti Suresh

Join the ASBMB Today mailing list

Sign up to get updates on articles, interviews and events.

Latest in Opinions

Opinions highlights or most popular articles

I’m fully vaccinated but feel sick – should I get tested for COVID-19?

I’m fully vaccinated but feel sick – should I get tested for COVID-19?

July 25, 2021

It’s impossible to know whether a vaccinated person is fully protected or could still develop a mild case if exposed to the coronavirus.

5 ways to use hip-hop in the classroom to build better understanding of science

5 ways to use hip-hop in the classroom to build better understanding of science

July 24, 2021

Teachers often don’t know how to make science relevant, and many students of color fail to develop a science identity.

What to ask during your faculty interview
Professional Development

What to ask during your faculty interview

July 21, 2021

“Going into your interview armed with good questions not only will help you gather intel to help you make the best decision for your career but also will help you stand above the competition.”

The STEM Academy: A necessary remedy to med school tunnel vision

The STEM Academy: A necessary remedy to med school tunnel vision

July 13, 2021

A one-week camp at the University of South Florida forged community as it introduced new students to the possibilities of a career in scientific research.

Merging biochemical and analytical training

Merging biochemical and analytical training

July 8, 2021

“(T)he pandemic revealed that while it is critical for us to specialize and have depth of knowledge in some domains, it is also essential that we cultivate some breadth in our skill set.”

Challenging science stereotypes with a video game

Challenging science stereotypes with a video game

July 7, 2021

Imagine a digital game set in a lab that creates a research experience accessible to all and populated by all.