The "voice" of the new corona virus? Scientists write according to their spike protein

Small nano-objects such as proteins or other molecules make up almost all living matter, including cells, tissues, viruses, and pathogens. Observing them generally requires sophisticated scientific instruments. However, there is now another novel form of expression that we can "listen" to.

　　
Markus J. Buehler is a McAfee engineering professor at Massachusetts Institute of Technology and a composer of experimental music, classical music, and electronic music. He is very interested in sound wave research. His works use a method called "material music", such as musical expressions derived from biological materials and life systems, in order to better understand basic science and mathematics.

　One of his research is to use music and sound design as a novel and abstract way to model, optimize and create new forms from bottom to top, and to evaluate the relationship between cross-system design. In his recent work, he developed a new framework for creating music based on proteins and other physical phenomena to explore the similarities and differences between different species, different scales, and physical models. At present, the outbreak of the new coronavirus in the United States, Buehler turned his attention to the spike protein of COVID-19, it is this protein that makes the new coronavirus so infectious.

　　He and his colleagues tried to reveal the vibration characteristics of the spike protein based on the pathogen, which may be a new way to study viruses. After converting COVID-19 into sound, it does not sound as deadly as we thought, just like a virus tricks our cells, the audio is as follows:

Figure | Audio converted from the new corona virus (Source: Soundcloud)

The music is about 1 hour and 50 minutes long, which is about the same as a classical concert. It shows some subtle relationships between life and death as opposite poles.

　　
The viral genome hijacks the host cell's protein manufacturing mechanism, forcing the host cell to replicate the viral genome and produce viral proteins, thereby producing new viruses from it. When you "listen" to viral proteins, you will find that complex designs produce incredibly interesting and relaxing sounds that do not convey the fatal impact of this protein on the world. Music, as a form of expression of this virus, also has a strong deceptive nature.

How to make the virus spectrum into "music"? The Buehler team developed a self-consistent sonic method for translating amino acid sequences into musical works, and used it in protein design based on artificial intelligence technology.

We heard COVID-19's "Music" is a multi-layered algorithm combination, including the vibration spectrum of the entire protein (expressed as sound and rhythm elements), the amino acid sequence and folds that make up the structure of the viral spike protein. The melody forming counterpoint music reflects the complex hierarchical geometry of proteins.

Figure | Translating COVID-19 spike protein into sound to visualize its vibration characteristics, which helps to find a way to stop the virus (Source: MIT News)

This research method calculates the auditory expression of each of the 20 natural amino acids based on the normal mode vibrations of protein amino acid building blocks, which is completely defined by the superposition of their respective natural vibrations. Following the musical concept of transposition equivalent, the vibration frequency is converted into an audible spectrum, and the music is played or written in a certain way to make it sound pitch or low while retaining the relationship between the tone or chord played.

This transposition method can ensure the relative value of the vibration frequency within each amino acid and between different amino acids. The characteristic spectrum and sound associated with each amino acid represent a musical scale composed of 20 tones, namely "amino acid scale" . To create a playable musical instrument, each tone related to amino acid is assigned to a specific key on the piano roll, which allows us to map the amino acid sequence in the protein to a musical score.

In order to reflect the high-level structural details of the protein, the volume, and duration of the notes associated with each amino acid are defined by the secondary structure of the protein, which is calculated using DSSP, thereby introducing musical rhythm. Then, the researchers trained a recurrent neural network-based on a large number of music scores generated by this ultrasonic processing the method, and generate music to capture the inherent relationship between the amino acid sequence and the protein structure.

The method proposed in this study can also provide a way to understand sequence patterns, mutations and provide an extended mechanism to explain the importance of protein sequences. This method can also provide insights into protein folding and understand the background of amino acid sequences when defining the secondary and higher-order folding structures of proteins, so it can be used to detect the effects of mutations in sound.

Figure | Converting the characteristic spectrum of amino acids into musical scales (Source: ACS)

What is the practical use of "music" to express the new coronavirus?

In an interview, Buehler stated that our brain is good at processing sounds. In one scan, our ears will hear all its level features: pitch, timbre, volume, melody, rhythm, and chords. If you want to see the same details in the image, you need a high-resolution microscope, and you can never see all the details at once. According to Buehler, the sound is a great way to access information stored in proteins.

Usually, the sound is made by vibrating a certain material, and music is made by arranging sound in layers. we can combine these concepts and use molecular vibration and neural networks to build new forms of music. We have been studying ways to transform protein structures into audible representations and convert these representations into new materials.

In the long run, converting proteins into sound provides scientists with another tool for understanding and designing proteins. For example, even small mutations can limit or enhance the pathogenicity of COVID-19. Through ultrasound conversion treatment, we can also compare the biochemical process of its spike protein with previous coronaviruses (such as SARS or MERS).

Based on this "music" creation, researchers can also analyze the vibration structure of the spike protein that infects the host, and understanding these vibration patterns is essential for drug design and other defenses against viruses. For example, such vibrations may change with increasing temperature. They can also tell us why COVID-19 is more likely to invade human cells than other viruses. Buehler and the team are still studying to explore these issues.

"We may also use a combination approach to design drugs that attack the virus. We can search for a new protein that matches the melody and rhythm of antibodies that can bind to spike protein, thereby interfering with its ability to infect." Buehler said.