YouSaid · the spoken record

Dmitry Korkin

lines on the record
124
first
2021-01-11
most recent
2021-01-11
sittings or episodes
1
sources
podcast

Every line below is reproduced as it was said and linked to the record it came from. Nothing here is summarised or generated. Directory · Search · Corrections

  1. “So, I mean, mutations are sort of a general way for these viruses to evolve, right? So it's essentially this is the way they evolve. This is the way they were able to jump from one species to another. We also see some recent jumps. There were some incidents of this virus jumping from human to dogs. So there is some danger in those jumps because every time it jumps it also mutates, right? So when it jumps to the species and jumps back, right? So it acquires some mutations that are sort of Driven by the environment of a new host. And it's different from the human environment. And so we don't know whether the mutations that are acquired in the new species are neutral with respect to the human host or maybe damaging.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  2. “Well, yeah, so it doesn't change, it doesn't evolve from the evolutionary perspective so drastically as, for example, the spike prote”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  3. “More attack surface, but from our analysis, from other evolution analysis, this protein is evolutionary more stable compared to the spike protein.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  4. “50 to 90. So, this is how this thing is organized. And so now typically, right? So you see the antibodies that target spike protein, certain parts of the spike protein, but there could be also some treatments, right? So these are small molecules that bind strategic parts of these proteins disrupting its functioning. One of the promising directions, it's one of the newest directions, is actually targeting the MDimer of the protein, targeting the proteins that make up this outer shell. Because if you're able to destroy the outer shell, you are essentially destroying the viral particle itself. So preventing it from functioning at the”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  5. “A single element of the single virus, single virus, right? And we have about roughly 50 to 90. Spike trimers, right? So when you show”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  6. “So those different proteins, they occur in different copies on the viral particle. So E, this pentomer complex, we only have two or three maybe per each particle. We have thousands or so of M dimers that essentially made up the entire outer shelf.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  7. “So the envelope is essentially the outer shell. Of the viral particle, the N denucleo capsid protein is something that is inside But get that, the n is likely to interact with m.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  8. “It's not understood. We are now, we've been working in the past six months since we met, actually, this is where we started working on trying to understand the overall. A structure of the envelope and the key components that made up this structure.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  9. “Exactly. And if you think about this, right? So this. Complex diviral shape needs to be organized somehow, self-organized somehow, right? So if it was a completely random process, you probably wouldn't have the envelope shell of the ellipsoid shape. You would have something pre-random shape. So there is some regularity in how this MDimers get attached to each other in a very specific directed way.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  10. “Now, there are also a very interesting direction in looking at the membrane, at the envelope portion of the protein and attacking its m protein. So there are, to give you a brief overview, there are four structural proteins. These are the protins that made up a structure of the virus. spike as protein that acts as a trimer so it needs three copies Envelope protein that acts as a pantomer, so it needs five copies. Act properly. M is the membrane protein. It forms dimers and actually it forms beautiful lattice. And this is something that we've been studying and we are seeing it in simulations. It actually forms a very nice grid or threads of different dimers attached next to each other. There's a bunch of copies of it.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  11. “So, I mean, there are many different implications to that. First of all, it's important to understand the virus itself, right? So in order to understand how it acts, what is the overall mechanistic process of this virus replication of this virus, proliferation to the cell? So that's one aspect. The other aspect is designing new treatments. So one of the possible treatments is designing nanoparticles. And so nanoparticles that will resemble the viral shape, that will have this spike integrated, and essentially would act as a competitor to the real virus by blocking the ACE2 receptors and thus preventing the real virus entering the cell.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  12. “So, CapSet is essentially the inner core of the viral particle where the RNA of the virus and it's protected by another protein and protein that essentially acts as a shield. Now we are learning more and more. So it's actually not just this shield is used for the stability of the outer shell of the virus. So it's pretty complicated.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  13. “Yeah, so it needs to be attached at least as far as I know. But when you get this thing attached on the surface, right, there is also a lot of dynamics on how it sits on the surface, right? So for example, there was a recent work again where people use the cry-electron microscopy to get the first glimpse of the overall structure. It's a very low res, but you still get some interesting details about the surface, about what is happening inside because we have literally no clue until recent work about how the capseit is organized.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  14. “It potentially can change the dynamics of because now you have two possible opportunities to get attached to the ACE2 receptor. It's a very complex molecular process, mechanistic process. But the first step of this process is the attachment of this spike protein, of the spike trimer to the human A2 receptor. So this is a molecule that sits on the surface of the human cell.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  15. “So, yes. And this is where Another level of complexity comes into play because right now what we see is we typically see just one of the arms going out. Getting ready to be attached to the ACE2 receptors. However, there was a recent mutation that people studied in that spike protein. Very recently a group from UMass Medical School. We happened to collaborate with group, so this is a group of Jeremy Luban and a number of other faculty. They actually solved the mutated structure of the spike and they showed that actually because of these mutations you have more than one Arms opening up And so now the frequency of two arms going up increase quite drastically.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  16. “Yeah, so people are still trying to understand the nature and the role of this one third. The top part, the primary function is to get attached to ACE2 receptor, human receptor. There is also beautiful mechanics of how this thing happens. So because there are three different copies of these chains, there are three different domains, right? So we're talking about domains. So this is the receptor binding domains, RBDs, that gets untangled and get ready to get attached to the receptor. And now they are not necessarily going in a sync mode. As a matter of fact, Of fact”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  17. “Mean, first of all, it's an incredibly challenging protein. And so we as a part of our sort of research to understand the structural basis of this virus, to sort of decode, structure decode every single protein in its proteome. We've been working on the spike protein and one of the main challenges was that CryM data allows us to reconstruct or to obtain the 3D coordinates of roughly two-thirds of the protein. It's a part that is buried into the membrane. Of the virus and of the viral envelope. And it also has a lot of unstable structures around it.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  18. “Exactly. We have these three chains, the three molecular chains coupled together and performing the function. That's when you look at this protein from the top, you see a perfect triangle. But other complexes are made up of different proteins. Some of them are completely different, some of them are similar. The hemoglobin molecule, right? So it's actually a protein complex. It's made of four basic subunits, two of them are identical to each other and two other identical to each other, but they are also similar to each other, which sort of gives us some ideas about the evolution of this molecule. And perhaps one of the hypotheses is that in the past, it was just Homo tetramer, right? So four identical copies, and then it became mutated over the time and became more.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  19. “Oh, yes. I mean, so it's a very complex structure and. We, you know, on top of the complexity of a single protein, right? So this structure actually is a complex, is a trimer. So it needs to form a trimer in order to function properly. So, a complex is agglomeration of multiple proteins. And so we can have the same protein copied in multiple copies and forming something that we call a homo oligomer means the same, right? So in this case, the spike protein is an example of a homotetrumer.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  20. “Shapes of much larger molecules, molecular complexes, just to give you one of the common examples for this year, right? So the first experimental structure of a SARS COVID-2 protein was the Cryam structure of the S protein. So the spike protein. And so it was solved very quickly and the reason for that is the advancement of this technology is pretty spectacular.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  21. “And so, because of that, the initial suspicion was that the proteins have globular shapes and the more of smaller proteins you obtain structurally, the more you became convinced that that's the case. And only later when we started having alternative approaches, the traditional ones are X-ray crystallography and NMR spectroscopy. So these are sort of the two main techniques that give us the 3D coordinates. But nowadays there's huge breakthrough in cryoelectron microscopy. So the more advanced methods that allow us to get into the 3D”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  22. “Well, you know, there are several perspectives on this. And one, of course, is the historical perspective, right? So historically, scientists have been able to structurally resolved, to obtain the 3D coordinates of a protein for smaller proteins. And smaller proteins tend to be a single domain protein. So we have a protein equal to a protein domain.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  23. “And in the past 20 years, scientists have been studying the nature of the protein domains because we realize that it's the unit. Because if you look at the functions, right? So many proteins have more than one function. And those protein functions are often carried out by those protein domains. We also see that in the evolution those proteins domains get shuffled. So they actually as a unit. Also from the structural perspective, right? Some people think of a protein as a sort of a globular molecule, but as a matter of fact, the globular part of this protein. Is a protein domain. So we often have this again, the collection of these protein domains align on a string as beads.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source

  24. “Yes and no. So the proteins indeed is the basic unit biological unit that carries out important function of the cell. However, through studying the proteins and comparing the proteins across different species, across different kingdoms, you realize that proteins are actually much more complicated. so-called modular complexity. And so what I mean by that is an average protein consists of several structural units. So we call them protein domains. And so you can imagine a protein as a string of beads where each bead is a protein domain.”

    2021-01-11 · Lex Fridman Podcast · #153 – Dmitry Korkin: Evolution of Proteins, Viruses, Life, and AI · IDENTIFIED FROM THE TRANSCRIPT · source