The discovery of protein’s power

8 minutes, 34 seconds Read

Luke Alesbrook prepares the test by loading the gas pistol. Image source: BBC

The University of Kent’s Light Gas Gun appears to be more like a lathe than a typical handgun, and it is a pretty large and complicated device.

Despite its cumbersome appearance, the Light Gas Gun at the University of Kent possesses remarkable capabilities.

It can propel projectiles at a staggering velocity of 1.5 kilometers per second, equivalent to roughly 3,500 miles per hour, surpassing the speed of a conventional bullet by nearly double.

In today’s experiment, the gun has been loaded with a small basalt rock fragment, slightly smaller than a pea, which will be forcefully propelled towards a specially formulated gel.

This gel consists of a refined and modified version of the protein talin, engineered to possess an extraordinary capacity to absorb impacts—an attribute we are about to witness firsthand.

As we are guided out of the gun room, a brief countdown precedes the moment when Luke Alesbrook, the gun operator, activates the trigger by pressing a button, initiating the launch.

Upon reentering the room, wisps of smoke drift from the gun barrel as the target area is examined. Remarkably, the gel, although visibly displaced, remains intact.

What proves crucial is that the metal plate positioned behind the gel exhibits no signs of damage. Without the protective gel, the forceful impact of the basalt would have undoubtedly caused a significant chunk to be torn from the plate.

Talin, responsible for this impressive force absorption, possesses unique mechanical properties.

Its structural composition comprises spirals of amino acids, the fundamental components of proteins, which intertwine to form bundles.

When subjected to tension, these bundles unfurl, extending the length of the protein by a factor of 10.

Upon the release of stress, the bundles promptly snap back into their original configuration, reminiscent of a spring’s behavior.

This remarkable ability allows talin to effectively absorb and distribute forces, safeguarding the metal plate from irreparable damage caused by the basalt projectile.

Professors Jennifer Hiscock, Ben Goult, and Amber Peswani are members of the shock-absorbing gel team (on the right).Image source: BBC

In order to understand the structure of talin and how it reacts to outside influences, Professor Ben Goult was essential.

They developed the idea of using talin as a material with remarkable shock-absorbing qualities in collaboration with Professor Jennifer Hiscock.

Professor Hiscock recalls chancely walking into Professor Goult’s office while he and another colleague were absorbed in a conversation about the extraordinary protein.

She suddenly thought of the brilliant idea of employing talin to make a bulletproof vest after seeing its enormous potential.

The event inspired them to work together to investigate the practical application of talin’s special properties in creating novel materials that may successfully reduce impact forces.

Commencing in 2016, their team embarked on the task of devising a method to interconnect talin proteins, creating a lattice-like structure akin to a net endowed with an almost whimsical capacity to stretch and rebound.

For Professor Goult, the journey has been a laborious one, having been immersed in unraveling talin’s mechanical properties and structural intricacies since 2005.

“It was far from a simple endeavor,” Professor Goult reflects.

“It demanded the collective efforts of a team consisting of six individuals working persistently over the course of four years to unravel the protein structure of talin.

Subsequently, an additional four years were dedicated to comprehending talin’s response to external forces.”

The combined efforts of their team spanned a substantial duration, reflecting the complexity and meticulousness required to unravel the secrets behind talin’s unique properties and behaviors.

Untangling the chains of amino acids that make up proteins is difficult. Image source: KAREN ARNOTT

Proteins indeed pose a formidable challenge when it comes to unraveling their complex molecular structures.

Comprising chains of amino acids, akin to beads on a string, the vast array of possibilities for their combinations can be bewildering.

With 20 naturally occurring amino acids or “beads” at play, the potential configurations are extensive.

Traditionally, determining protein structures relied on techniques such as electron microscopy and X-ray crystallography, processes that could span several years to complete.

However, in recent times, the advent of artificial intelligence (AI) has brought about a revolution in this domain.

AI has significantly transformed the process by enabling the prediction of protein structures for hundreds of millions of proteins.

This breakthrough has opened up new avenues for accelerating and expanding our understanding of protein structures, leading to advancements in various scientific disciplines.

The outstanding result of AlphaFold in CASP 14 (Critical Assessment of Protein Structure Prediction), a biennial competition that assesses various computer systems’ capacity to predict protein structures, marked a turning point in November 2020.

AlphaFold not only outperformed other algorithms but also proved to be incredibly accurate at predicting protein structures.

It made important advancements in the field of protein structure prediction with predictions that significantly outperformed those of its competitors.

Within the scientific world, this accomplishment received a great deal of attention and praise since it demonstrated the enormous potential of artificial intelligence and its capacity to fundamentally alter our understanding of protein structures.

Numerous scientific fields now have new opportunities for research and application because to AlphaFold’s innovations.

 

AlphaFol’s development was assisted by Kathryn Tunyasuvunakool. Image source: BEN CATCHPOLE

One of AlphaFold’s developers from DeepMind, the AI subsidiary of Alphabet (Google’s parent company), Kathryn Tunyasuvunakool, discusses the astounding results of the program’s performance at CASP 14.

She acknowledges that the group is aware of their encouraging internal CASP results. Regarding the performance of the other competing groups, there was still some ambiguity.

Therefore, it was a nice surprise when AlphaFold’s advantage over the other contestants turned out to be far greater than expected.

The team was shocked by the unanticipated size of AlphaFold’s accomplishment, underscoring the fact that it was a ground-breaking feat.

AlphaFold’s outstanding result at CASP 14 showed the technology’s enormous potential for revolutionizing protein structure prediction and setting new standards.

The exceptional performance of AlphaFold2 in the previous competition led to a significant impact on subsequent events.

In the subsequent competition, all the top-performing teams adopted versions of AlphaFold, recognizing its unparalleled capabilities.

The influence of AlphaFold and its subsequent iterations has been transformative for the database of protein structures.

It has expanded from a mere few hundred thousand to encompass hundreds of millions of structures.

This wealth of structural information has presented a tremendous boon for scientists and researchers, particularly in fields like drug development.

The availability of such an extensive database allows for rapid identification of proteins with promising structures for specific applications, such as binding to cancer cells.

This accelerated pace of research has unlocked new possibilities and opportunities, propelling advancements in various scientific endeavors and bringing us closer to potential breakthroughs in medicine and other domains.

AlphaFold has restrictions, though. Because proteins frequently interact with other molecules, AlphaFold can currently only predict the protein portion of how a protein will function.

Additionally, proteins are dynamic molecules that change shape, as Professor Goult discovered with talin. Researchers can get a static image from AlphaFold, but it cannot model those changes.

Additionally, researchers could seek to create new proteins from scratch to carry out particular functions. Prof. David Baker, director of the Institute for Protein Design at the nearby University of Washington, has that as his main area of interest.

According to David Baker, protein research is “an extremely exciting area.” Image source: University of Washington

Professor Ben Goult’s team has indeed developed an artificial intelligence system called RF Diffusion, which utilizes the principles of DALL-E, an AI known for generating unique visual content.

RF Diffusion, however, is focused on protein design rather than image generation.

It was trained by deconstructing well-known proteins and subsequently reassembling them in a step-by-step manner.

Scientists can leverage RF Diffusion to specify desired properties for a new protein.

For example, they can seek proteins with specific capabilities, such as the ability to bind to a particular target or act as a catalyst for a specific chemical process.

By employing RF Diffusion, researchers can explore the protein design space, accelerating the discovery of novel proteins with tailored properties that have applications in various domains, including targeted therapies and catalysis.

Indeed, with RF Diffusion, scientists have the ability to input their desired specifications for a protein, and the AI system generates a protein structure that aligns with those specifications.

This capability marks a notable advancement beyond the existing state of the art in protein design.

Professor Baker, recognizing the significance of RF Diffusion, emphasizes the immense potential that arises from designing proteins to address a wide range of challenges.

The versatility and applicability of custom-designed proteins hold tremendous promise in solving various problems across different scientific disciplines.

This breakthrough in protein design opens up new avenues for innovation and discovery, paving the way for potential advancements in fields such as medicine, bioengineering, and more.

Professor Baker recognizes the vast potential of protein design in various fields, including the development of novel therapies for cancer, neurological disorders, and infectious diseases.

Additionally, the creation of catalysts that can enhance reaction rates and efficiency holds significant value for industrial applications.

Moreover, Professor Baker acknowledges that protein research may lead to the emergence of entirely new materials with unique properties and functionalities.

The wide-ranging opportunities presented by protein research make it an appealing and exciting career choice for young scientists who are embarking on their professional journeys.

In Professor Baker’s view, the current state of protein research is remarkably stimulating, positioning it as one of the most captivating and dynamic fields of science.

The possibilities for innovation and discovery within protein research are abundant, attracting young scientists and offering them an opportunity to contribute to groundbreaking advancements and shape the future of scientific knowledge.

With funding from the Ministry of Defence, Professors Goult and Hiscock are attempting to increase production of their protein talin back in Kent.

Making enough of their shock-absorbing gel is intended to support a larger test. The Kent researchers believe their gel will eventually be able to lessen the amount of heavy ceramic currently utilized in bulletproof plates.

Prof. Hiscock continues to be in awe of how their protein gel forms for the time being.

The spontaneity of the process and the ability of all those molecules to combine to create fibrous networks make it attractive.

Similar Posts

Leave a Reply

Your email address will not be published. Required fields are marked *