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

Lex Fridman talks with Dmitry Korkin in his second appearance about the modular complexity of proteins, the structure and mechanics of the SARS-CoV-2 virus, and how viruses mutate and jump between species. They explore the origin and evolution of life, the Drake equation and the possibility of alien life, and the history of AI from expert systems to modern machine learning. Korkin assesses DeepMind's AlphaFold 2 and whether protein folding is truly 'solved,' arguing it works for compact single domains but multi-domain and multi-protein folding remain far harder. The conversation closes with concerns about engineered pandemics, book recommendations, and a Russian poem read by heart.

• Korkin argues AlphaFold's success echoes the old expert systems: its power comes from building deep domain knowledge into the model.
  01:04:46
• He calls DeepMind's AlphaFold 2 announcement essentially 'a blog post written by a marketing team,' cautioning against treating it as a published paper.
  01:17:49
• He pushes back on 'protein folding is solved': AlphaFold mainly cracks compact single/two-domain proteins, while multi-domain proteins remain far from understood.
  01:18:20
• Korkin ranks AlphaFold among his top three AI breakthroughs, but places Deep Blue beating Kasparov as the most groundbreaking moment in AI history.
  01:24:34
• He reveals his lab is building a machine learning model to predict whether a viral strain is pathogenic from its sequence.
  01:42:14
• Asked who designs better viruses, nature or humans, he says he'd still be more worried about natural pandemics than engineered ones.
  01:49:02
• Folding begins before a protein is fully made, starting as it emerges from the ribosome, which he calls one of biology's biggest enigmas.
  01:08:55
• Korkin recounts asking a 'dumb question' on a chemistry forum and waking up to a reply from Nobel laureate Joshua Lederberg.
  00:57:58

• Proteins are modular: an average protein is like a string of beads where each bead is a structural, functional, and evolutionary unit called a domain.
  00:02:37
• The first experimental structure of a SARS-CoV-2 protein, the spike, was solved very quickly thanks to advances in cryo-electron microscopy.
  00:06:19
• A single virus particle is mostly made of about a thousand M-protein dimers forming the outer shell, plus roughly 50 to 90 spike trimers.
  00:18:26
• A promising new attack vector is targeting the M dimer outer shell, which is evolutionarily more stable than the spike protein.
  00:19:29
• A 2018 Nature paper reported the amino acid glycine found in comet dust, hinting at the cosmic chemistry of life's building blocks.
  00:46:29
• The rare earth hypothesis counters the Drake equation, arguing Earth's conditions may be nearly unique in the galaxy or universe.
  00:48:36
• Joshua Lederberg's 1960s DENDRAL project, an expert system to identify molecules from mass spec data, helped originate modern bioinformatics.
  01:00:36
• Korkin argues all intelligence is some form of search, and that search is an integral but currently undervalued part of AI.
  01:26:38
• Computational biophysicists first won a Nobel Prize for protein folding work back in 2013.
  01:39:36
• Von Neumann wrote 'The Computer and the Brain' while dying of cancer; it was published in 1958, a year after his 1957 death.
  02:01:35

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