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Translating proteins into music, and back

Translating proteins into music, and back – Listen to Protein Music

Want to create a brand new type of protein that might have useful properties? No problem. Just hum a few bars.

In a surprising marriage of science and art, researchers at MIT have developed a system for converting the molecular structures of proteins, the basic building blocks of all living beings, into audible sound that resembles musical passages. Then, reversing the process, they can introduce some variations into the music and convert it back into new proteins never before seen in nature.

The new method translates an amino acid sequence of proteins into this sequence of percussive and rhythmic sounds. Courtesy of Markus Buehler.

Although it’s not quite as simple as humming a new protein into existence, the new system comes close. It provides a systematic way of translating a protein’s sequence of amino acids into a musical sequence, using the physical properties of the molecules to determine the sounds. Although the sounds are transposed in order to bring them within the audible range for humans, the tones and their relationships are based on the actual vibrational frequencies of each amino acid molecule itself, computed using theories from quantum chemistry.

The system was developed by Markus Buehler, the McAfee Professor of Engineering and head of the Department of Civil and Environmental Engineering at MIT, along with postdoc Chi Hua Yu and two others. As described today in the journal ACS Nano, the system translates the 20 types of amino acids, the building blocks that join together in chains to form all proteins, into a 20-tone scale. Any protein’s long sequence of amino acids then becomes a sequence of notes.

While such a scale sounds unfamiliar to people accustomed to Western musical traditions, listeners can readily recognize the relationships and differences after familiarizing themselves with the sounds. Buehler says that after listening to the resulting melodies, he is now able to distinguish certain amino acid sequences that correspond to proteins with specific structural functions. “That’s a beta sheet,” he might say, or “that’s an alpha helix.”

Learning the language of proteins

The whole concept, Buehler explains, is to get a better handle on understanding proteins and their vast array of variations. Proteins make up the structural material of skin, bone, and muscle, but are also enzymes, signaling chemicals, molecular switches, and a host of other functional materials that make up the machinery of all living things. But their structures, including the way they fold themselves into the shapes that often determine their functions, are exceedingly complicated. “They have their own language, and we don’t know how it works,” he says. “We don’t know what makes a silk protein a silk protein or what patterns reflect the functions found in an enzyme. We don’t know the code.”

By translating that language into a different form that humans are particularly well-attuned to, and that allows different aspects of the information to be encoded in different dimensions — pitch, volume, and duration — Buehler and his team hope to glean new insights into the relationships and differences between different families of proteins and their variations, and use this as a way of exploring the many possible tweaks and modifications of their structure and function. As with music, the structure of proteins is hierarchical, with different levels of structure at different scales of length or time.

The team then used an artificial intelligence system to study the catalog of melodies produced by a wide variety of different proteins. They had the AI system introduce slight changes in the musical sequence or create completely new sequences, and then translated the sounds back into proteins that correspond to the modified or newly designed versions. With this process they were able to create variations of existing proteins — for example of one found in spider silk, one of nature’s strongest materials — thus making new proteins unlike any produced by evolution.

The percussive, rhythmic, and musical sounds heard here are generated entirely from amino acid sequences. Courtesy of Markus Buehler.

Although the researchers themselves may not know the underlying rules, “the AI has learned the language of how proteins are designed,” and it can encode it to create variations of existing versions, or completely new protein designs, Buehler says. Given that there are “trillions and trillions” of potential combinations, he says, when it comes to creating new proteins “you wouldn’t be able to do it from scratch, but that’s what the AI can do.”

“Composing” new proteins

By using such a system, he says training the AI system with a set of data for a particular class of proteins might take a few days, but it can then produce a design for a new variant within microseconds. “No other method comes close,” he says. “The shortcoming is the model doesn’t tell us what’s really going on inside. We just know it works.”

This way of encoding structure into music does reflect a deeper reality. “When you look at a molecule in a textbook, it’s static,” Buehler says. “But it’s not static at all. It’s moving and vibrating. Every bit of matter is a set of vibrations. And we can use this concept as a way of describing matter.”

The method does not yet allow for any kind of directed modifications — any changes in properties such as mechanical strength, elasticity, or chemical reactivity will be essentially random. “You still need to do the experiment,” he says. When a new protein variant is produced, “there’s no way to predict what it will do.”

The team also created musical compositions developed from the sounds of amino acids, which define this new 20-tone musical scale. The art pieces they constructed consist entirely of the sounds generated from amino acids. “There are no synthetic or natural instruments used, showing how this new source of sounds can be utilized as a creative platform,” Buehler says. Musical motifs derived from both naturally existing proteins and AI-generated proteins are used throughout the examples, and all the sounds, including some that resemble bass or snare drums, are also generated from the sounds of amino acids.

The researchers have created a free Android smartphone app, called Amino Acid Synthesizer, to play the sounds of amino acids and record protein sequences as musical compositions.

“Markus Buehler has been gifted with a most creative soul, and his explorations into the inner workings of biomolecules are advancing our understanding of the mechanical response of biological materials in a most significant manner,” says Marc Meyers, a professor of materials science at the University of California at San Diego, who was not involved in this work.

Meyers adds, “The focusing of this imagination to music is a novel and intriguing direction. This is experimental music at its best. The rhythms of life, including the pulsations of our heart, were the initial sources of repetitive sounds that engendered the marvelous world of music. Markus has descended into the nanospace to extract the rythms of the amino acids, the building blocks of life.”

“Protein sequences are complex, as are comparisons between protein sequences,” says Anthony Weiss, a professor of biochemistry and molecular biotechnology at the University of Sydney, Australia, who also was not connected to this work. The MIT team “provides an impressive, entertaining and unusual approach to accessing and interpreting this complexity. … The approach benefits from our innate ability to hear complex musical patterns. Through harmony and discord, we now have an entertaining and useful tool to compare and contrast amino acid sequences.”

Materials provided by Massachusetts Institute of Technology

Neonatal intensive-care unit

Researchers find music beneficial for the development of brains of premature infants

Even before birth, human beings can listen to music. In addition to it, babies in the intensive care unit have a very sensitive ear. This can have a negative effect on their growing brains as the noises of the surroundings can bring unexpected stress.

It has been estimated that almost half of the babies born before the 32nd week in pregnancy will be later diagnosed with brain disorders which can be related to attention or emotional problems. A number of studies have shown that during this critical time, exposure to music can help in stabilizing the heart rate and breathing of a premature baby. It can also improve sleeping and eating patterns.

Music is essentially sound form which is organised in time. A team of scientists in Switzerland have been testing the effects of music to protect the brain and they conducted a double-blind study on the musical effects in the neonatal ICU, whose initial results are quite promising. The study has been published in PNAS.

The premature babies who were born almost four months before their schedule were treated to a daily dose of music which was specially meant for them. Their brain functions showed better development than the ones who were not treated to music. Lara Lordier, a co-author in this study and a researcher at the University of Geneva and University Hospitals of Geneva said that the team arranged the various parts of the day with different types of music. A music to accompany when they wake up, one to interact with them while they are awake and also in their sleeping phase. The study was conducted on 24 full-term babies and 39 premature babies.

Out of 39 premature ones, 20 were treated to the musical intervention. They received approximately eight minutes of very soothing music consisting of bells, harps. The snake charmer’s flute of India was also played during the week five times, which incidentally had the maximum soothing effect on the babies.

With the help of functional MRI on all the three groups of infants, researchers found that neural networks of the children who were exposed to music had higher functional connectivity and the network resembled the full-term babies. The premature babies who listened to music had improved brain salience network and their auditory, sensory, thalamus networks were also improved. While those babies who were not treated to the music had poor functional connectivity.

It is crucial to take care of the babies’ brains in the intensive care unit in a proper strategic way since the brains are still immature. As the age of the participants reaches six, researchers will be able to test whether the cognitive benefits of the music have stuck with them through the years.