Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI | Lex Fridman Podcast #153 | Summary and Q&A

TL;DR

Proteins, the basic building blocks of life, consist of modular protein domains, and understanding their evolution and folding process is crucial for various applications, including developing treatments and studying extraterrestrial life.

Key Insights

• 🧬 Proteins are the basic building blocks of life, but they are more complex than initially thought, with many proteins consisting of multiple structural units called protein domains.
• 🔍 Protein domains play a crucial role in protein structure and function, with different domains often responsible for different functions within a protein.
• 🌐 Proteins can be visualized as a string of protein domains, like beads on a string, with each domain made up of amino acid residues.
• 🌍 The study of protein evolution and the modular complexity of proteins has provided insights into the origins and diversity of life on Earth.
• 🦠 Viruses are both terrifying and beautiful, threatening human civilization while also giving us insights into the nature of life on Earth.
• 🔬 Understanding the structure and function of proteins, including the spike protein of SARS-CoV-2, is crucial for developing treatments and vaccines.
• 💡 Dmitry Korkin had a personal encounter with Joshua Lederberg, an influential scientist known for his work on bacterial genetics, extraterrestrial life, and expert systems.
• ⚙️ Expert systems, including Joshua Lederberg's Dandruff project, were early attempts at combining chemistry and computer science to study extraterrestrial molecules. They laid the groundwork for modern bioinformatics and AI.
• 🧩 DeepMind's AlphaFold2, which recently "solved" protein folding, has the potential to dramatically advance our understanding of protein structure and function, providing valuable insights for drug design and disease treatment.

Transcript

the following is a conversation with dmitry korkin his second time in the podcast he's a professor of bioinformatics and computational biology at wpi where he specializes in bioinformatics of complex disease computational genomics systems biology and biomedical data analytics he loves biology he loves computing plus he is russian and recites a poem... Read More

Questions & Answers

Q: How do protein domains contribute to the complexity and functionality of proteins?

Protein domains are essential building blocks of proteins that carry out specific functions and provide structural stability. They can interact with other domains to create complex protein structures and enable diverse protein functions.

Q: What role does protein folding play in understanding diseases and developing treatments?

Protein folding is crucial in understanding how proteins misfold and cause diseases. By studying protein folding, researchers can identify potential targets for developing treatments and interventions to correct protein misfolding and associated diseases.

Q: How does protein structure prediction using machine learning, like AlphaFold, revolutionize protein science?

Machine learning-based protein structure prediction, such as AlphaFold, has significantly advanced our ability to predict protein structures, which is essential for understanding protein functions and designing treatments. By accurately predicting protein structures, scientists can gain deeper insights into protein folding and its relationship to biological processes.

Q: What are the potential implications of finding extraterrestrial life and studying their proteins?

Discovering extraterrestrial life and studying their proteins could have profound implications for our understanding of the origin of life and the possibilities of life beyond Earth. It could provide insights into the diversity of proteins and expand our knowledge of the biochemical processes occurring in the universe. Additionally, it could potentially lead to advances in biotechnology and medicine.

Summary

In this conversation, Dmitry Korkin, a professor of bioinformatics and computational biology, discusses proteins as the building blocks of life, their modular complexity, and the importance of protein domains. He also talks about the spike protein of the SARS-CoV-2 virus, its complex structure, and potential implications for treatment development. Dmitry delves into the evolution of proteins and the role of modularity, as well as the concept of alternative splicing. The conversation touches on the possibility of evolutionary processes in computer programs and the origins of life on Earth.

Questions & Answers

Q: Are proteins considered the basic building blocks of life?

Yes and no. While proteins are the fundamental units that carry out important cellular functions, they are more complex than initially thought. Proteins consist of several structural units known as protein domains, which are like beads on a string. Protein domains often have different functions, and the shuffling of these domains during evolution contributes to the complexity of proteins.

Q: Why aren't protein domains discussed as often in popular culture?

Historically, scientists focused on structurally resolving smaller proteins, which tend to be single-domain proteins. This led to the misconception that proteins are globular in shape. However, advancements in cryo-electron microscopy have allowed researchers to study the 3D shape of larger protein complexes, revealing the significance of protein domains. The historical perspective and limited structural data contribute to the underrepresentation of protein domains in popular culture.

Q: How many domains does the spike protein of SARS-CoV-2 have?

The spike protein of SARS-CoV-2 is a complex structure composed of multiple domains. Specifically, it is a trimer, meaning it consists of three identical copies of the protein chain. The exact number of domains within the spike protein is not mentioned, but it is a highly intricate structure with various components.

Q: Is the spike protein of SARS-CoV-2 capable of floating on its own, or does it require interaction with the membrane?

The spike protein requires attachment to the human ACE2 receptor, which is a molecule on the surface of human cells. It needs to be attached to the receptor to initiate the process of viral encapsulation. The attachment and interaction of the spike protein with the membrane is crucial for its functioning.

Q: Is there something interesting or beautiful about the spike protein of SARS-CoV-2?

The spike protein is an incredibly challenging protein to study. Understanding its structural basis and decoding its function is essential in combating the virus. Recent studies have revealed the complexity of the spike protein, such as its trimeric structure and asynchronous behavior of the receptor binding domains. Mutations in the spike protein can also affect the dynamics and attachment to ACE2 receptors, potentially altering the virus's behavior.

Q: What are the implications of studying the structure and function of the spike protein for developing vaccines or treatments?

Studying the virus's structural and functional aspects, including the spike protein, is crucial for understanding its replication and mechanisms. This knowledge can aid in developing treatments and designing nanoparticles that compete with the virus, blocking ACE2 receptors and preventing viral entry into cells. Another promising direction is targeting the outer shell of the viral particle by disrupting the membrane protein (M protein), which is an important component for overall stability.

Q: Are you worried about the mutations in the virus, such as the recent ones in the UK and South Africa?

Mutations are a common aspect of viral evolution, allowing viruses to adapt and jump between different species. While mutations can be worrisome, there is no substantial evidence suggesting aggressive mutations that make the virus resistant to vaccines or treatments. However, it is essential to study the virus's evolution and the mechanisms that drive it to ensure we stay ahead in developing effective treatments and vaccines.

Q: How do proteins evolve from a common ancestor to the diverse proteins we observe today?

Protein evolution is characterized by modularity, meaning proteins consist of functional and evolutionary building blocks known as protein domains. Evolution preserves the stability and function of these domains, allowing them to persist across different proteins and species. Protein domains contribute to the hierarchical complexity of proteins, with linkers connecting these domains. Alternative splicing introduces additional complexity, where a single gene can give rise to multiple protein products with different functional properties.

Q: Do you think we'll ever have computer programs that undergo an evolutionary process similar to biological evolution?

While the evolution of computer programs is not yet comparable to biological evolution, there is the potential for computer programs to exhibit evolutionary-like behavior. Evolutionary algorithms already exist to optimize searches and simulate recombination and mutation. Additionally, researchers explore nature-inspired algorithms and the interplay between biological and artificial systems. The future may see the emergence of more sophisticated programs that replicate and evolve in digital and physical spaces.

Q: What are your thoughts on the probability of life emerging on habitable planets?

The probability of life emerging on habitable planets is an open question. Recent discoveries of simple amino acids on comets suggest that the building blocks for life can be present in extraterrestrial environments. However, the exact probability is uncertain, and factors such as the rare earth hypothesis propose that Earth's conditions are unique or rare. While Earth may not be entirely unique, the chances of life emerging remain reasonably small.

Q: How difficult is it to estimate the probability of life emerging on Earth and other habitable planets?

Estimating the probability of life's emergence is challenging due to the many variables involved. The specific conditions necessary for life's emergence are not entirely understood, and the rarity of certain conditions, as proposed by the rare earth hypothesis, adds another layer of complexity. Intuition and scientific knowledge suggest that while not impossible, the chances of life emerging are not extremely high. Further research and exploration are necessary to gain a better understanding of life's origins.

Summary & Key Takeaways

• Proteins are the basic units carrying out essential functions in cells, but they are complex entities consisting of modular protein domains.

• Protein domains serve as functional and structural building blocks, and their interactions and folding process play a crucial role in protein function.

• Understanding protein folding and evolution is important for various areas, including developing treatments, studying protein-protein interactions, and potentially exploring extraterrestrial life.