Why is it in the news?

• Proteins are crucial for all living organisms, playing a vital role in nearly every biological process. Their complexity has made them a focus of scientific research for decades, leading to significant breakthroughs that have earned numerous Nobel Prizes.
• This year’s Nobel Prize in Chemistry recognizes David Baker, Demis Hassabis, and John Jumper—not for new insights into proteins, but for developing tools that simplify and accelerate the understanding of protein structures and the creation of novel proteins.

The Role of AlphaFold

• Hassabis and Jumper share half of the prize for creating AlphaFold, an AI tool that accurately predicts protein structures.
• Baker, who received the other half, utilized similar computational methods to design new proteins that do not exist in nature but serve useful functions. Together, they have achieved goals that scientists have pursued for decades.

Understanding Protein Structure

• Proteins are composed of long chains of amino acids, which are organic molecules made of carbon, hydrogen, nitrogen, oxygen, and sometimes sulfur.
• There are 20 different amino acids that act as the building blocks of proteins, and their specific sequences fold into unique three-dimensional shapes essential for various biological functions.
• Some proteins, known as enzymes, accelerate biochemical reactions, while others provide structural support or assist in immune responses.
• The structure of proteins determines their function. Decades ago, it was discovered that the amino acid sequence dictates how proteins fold, a finding that earned Christian Anfinsen the Chemistry Nobel in 1972.
• Balram, former director of the Indian Institute of Science, emphasized the need to understand the “grammar” of amino acid arrangements, which has proven challenging.

Challenges in Decoding Proteins

• Progress in decoding protein structures has been slow, as traditional methods like X-ray crystallography are labour-intensive and time-consuming. Nevertheless, thousands of protein structures and amino acid sequences have been cataloged.
• Hassabis and Jumper built on this foundation to create AlphaFold, which uses known sequences to predict protein structures with impressive accuracy. Since its development, AlphaFold has undergone multiple upgrades and is widely used in research.

Innovations in Synthetic Proteins

• Baker’s approach differs by designing entirely new, synthetic proteins that do not occur in nature. He produces new amino acid sequences that form valid proteins capable of performing useful functions, akin to constructing new sentences.
• For instance, synthetic proteins could be designed to degrade non-biodegradable plastics. Traditional methods for creating synthetic proteins can be lengthy, involving evolutionary processes that take years. Baker’s method is significantly more efficient.

Implications for Drug Discovery

The work of these scientists has far-reaching implications for drug discovery and addressing diseases related to protein disorders.