Q: What’s the benefit of translating proteins into sound?
A: Our brains are great at processing sound! In one sweep, our ears pick up all of its hierarchical features: pitch, timbre, volume, melody, rhythm, and chords. We would need a high-powered microscope to see the equivalent detail in an image, and we could never see it all at once. Sound is such an elegant way to access the information stored in a protein.
Typically, sound is made from vibrating a material, like a guitar string, and music is made by arranging sounds in hierarchical patterns. With AI we can combine these concepts, and use molecular vibrations and neural networks to construct new musical forms. We’ve been working on methods to turn protein structures into audible representations, and translate these representations into new materials.
Q: What can the sonification of SARS-CoV-2's "spike" protein tell us?
A: Its protein spike contains three protein chains folded into an intriguing pattern. These structures are too small for the eye to see, but they can be heard. We represented the physical protein structure, with its entangled chains, as interwoven melodies that form a multi-layered composition. The spike protein’s amino acid sequence, its secondary structure patterns, and its intricate three-dimensional folds are all featured. The resulting piece is a form of counterpoint music, in which notes are played against notes. Like a symphony, the musical patterns reflect the protein’s intersecting geometry realized by materializing its DNA code.
Q: What did you learn?
A: The virus has an uncanny ability to deceive and exploit the host for its own multiplication. Its genome hijacks the host cell’s protein manufacturing machinery, and forces it to replicate the viral genome and produce viral proteins to make new viruses. As you listen, you may be surprised by the pleasant, even relaxing, tone of the music. But it tricks our ear in the same way the virus tricks our cells. It’s an invader disguised as a friendly visitor. Through music, we can see the SARS-CoV-2 spike from a new angle, and appreciate the urgent need to learn the language of proteins.
Q: Can any of this address Covid-19, and the virus that causes it?
A: In the longer term, yes. Translating proteins into sound gives scientists another tool to understand and design proteins. Even a small mutation can limit or enhance the pathogenic power of SARS-CoV-2. Through sonification, we can also compare the biochemical processes of its spike protein with previous coronaviruses, like SARS or MERS.
In the music we created, we analyzed the vibrational structure of the spike protein that infects the host. Understanding these vibrational patterns is critical for drug design and much more. Vibrations may change as temperatures warm, for example, and they may also tell us why the SARS-CoV-2 spike gravitates toward human cells more than other viruses. We’re exploring these questions in current, ongoing research with my graduate students.
We might also use a compositional approach to design drugs to attack the virus. We could search for a new protein that matches the melody and rhythm of an antibody capable of binding to the spike protein, interfering with its ability to infect.
Q: How can music aid protein design?
A: You can think of music as an algorithmic reflection of structure. Bach’s Goldberg Variations, for example, are a brilliant realization of counterpoint, a principle we’ve also found in proteins. We can now hear this concept as nature composed it, and compare it to ideas in our imagination, or use AI to speak the language of protein design and let it imagine new structures. We believe that the analysis of sound and music can help us understand the material world better. Artistic expression is, after all, just a model of the world within us and around us.
