Well deserved! Especially for Alphafold. It is the most impactful invention in structural biology this century along with Cryo-EM.
tldr on Cryo-EM?
Chemistry Nobel: Computational protein design and protein structure prediction
331–340 of 343 posts
Re: Chemistry Nobel: Computational protein design and protein structure prediction
#332As a computer scientist who is oppositional to AGI boom-bubble mania, it was easy to decry the Nobel in physics. But, contextually given who Murray Gell-Mann was and what field he was in (astrophysics) I feel a very strong Gell-Mann Effect here because I am happy to accept THIS use of computational systems to advance (bio)chemistry is worthy, and I find myself wondering why I am so uncritical about it?
Alpha fold gives a definite advance in our understanding of the world, chatgpt and similar not so much?
I'd take this on advice. Anything else for me would be post-hoc rationale to what was simply taken on trust!
Re: Chemistry Nobel: Computational protein design and protein structure prediction
#333Earlier quoted context omitted.
I... Don't think that's right? Although I would appreciate being corrected with some good sources on this. It's a fast moving field and combinatorial chemistry is still new enough that many recently published structures wouldn't have used it. I'm well aware of the impact of natural products and particularly plant secondary metabolites in drug discovery. I'm also aware of combinatorial synthesis occasionally hitting s…
Perhaps we are using "structure" in different senses. Yes, it is possible to generate a molecule with a chemical structure unlike any biological molecule and have it bind to a protein, but it can only do so if its 3D structure is analogous to what naturally binds there. Natural products are a source of drugs because evolution has already done this work for us.
https://en.wikipedia.org/wiki/Functional_analog_(chemistry) explains the difference between structural and functional analogs: fentanyl is quite dissimilar from morphine, but binds the same targets.
Re: Chemistry Nobel: Computational protein design and protein structure prediction
#334Earlier quoted context omitted.
Perhaps we are using "structure" in different senses. Yes, it is possible to generate a molecule with a chemical structure unlike any biological molecule and have it bind to a protein, but it can only do so if its 3D structure is analogous to what naturally binds there. Natural products are a source of drugs because evolution has already done this work for us.
https://en.wikipedia.org/wiki/Functional_analog_(chemistry) explains the difference between structural and functional analogs: fentanyl is quite dissimilar from morphine, but binds the same targets.
Yes, the chemical structures can look very different when drawn in the 2D manner, but that's why 2D structures aren't very useful for understanding binding, much as primary sequences of proteins aren't that useful. Morphine and fentanyl bind to μ-opioid receptors, just like what naturally binds there (endorphins and enkephalin). But if they are binding to the same receptor, they have to have similar structures in the biologically meaningful 3D sense (at least where they bind).
Re: Chemistry Nobel: Computational protein design and protein structure prediction
#335Earlier quoted context omitted.
> this is what I mean by "a shitty answer fast" - structure prediction isn't a canonical answer A proper protein structural model is an all-atom representation of the macromolecule at its global minimum energy conformation, and the expected end result of the folding process; both are equivalent and thus equally canonical. The “fast” part, i.e., the decrease in computational time comes mostly from the heuristics used…
Most proteins don't fold to their global energy minimum- they fold to a collection of kinetically accessible states. Many proteins fail to reach the global minimum because of intermediate barriers from states that are easily reached from the unfolded state. Attempting to predict structures using mechanism that simulate the physical folding process waste immense amount of energy and time sampling very uninteresting ar…
Except, you know, if you're trying to understand the physical folding process...
There are lots of enhanced sampling methods out there that get at the physical folding process without running just vanilla molecular dynamics trajectories.
Re: Chemistry Nobel: Computational protein design and protein structure prediction
#336Earlier quoted context omitted.
I'm always interested in hearing about these people who go and get a PhD in an unrelated field to their original studies, often years after leaving university and working in an industry. Here it says Hasabis did an undergraduate degree in a computer science program, and them spent a decade working on computer games at studios, and then somehow just rocked up to a university and asked to do a PhD in neuroscience. I fe…
> tried to go back and ask to do a PhD in, say, Physics - I'd be promptly told to go fuck myself Only if you need money. If you pay the tuition they'll receive you with open arms. I've seen this for a guy is his mid to late 30s. As everything in the states, it's completely pay to play and largely pay to win.
What? Physics programs don't work like that, at least not T1-2 ones I know about. A physics PhD is not pay to play and anyone thinking it is would fail out on their qual at every university I'm familiar with.
Re: Chemistry Nobel: Computational protein design and protein structure prediction
#337Earlier quoted context omitted.
So can we expect that Sam Altman will be honored with Nobel prize 2025? After all physics prize went to AI researchers this year, and chemistry prize went to an organizational head.
You're really conflating things. Altman is no Hassabis. Just because there is a ton of hype from OpenAI doesn't detract from what DeepMind has done. AlphaGo anybody? Are we really already forgetting what a monumental problem protein folding was, decades of research, and AlphaFold came in and revolutionized it overnight. We are pretty jaded these days when miracles are happening all the time and people are like "yeah,…
Nitpick - this is protein structure prediction, not protein folding
Re: Chemistry Nobel: Computational protein design and protein structure prediction
#338Earlier quoted context omitted.
You're really conflating things. Altman is no Hassabis. Just because there is a ton of hype from OpenAI doesn't detract from what DeepMind has done. AlphaGo anybody? Are we really already forgetting what a monumental problem protein folding was, decades of research, and AlphaFold came in and revolutionized it overnight. We are pretty jaded these days when miracles are happening all the time and people are like "yeah,…
Nitpick - this is protein structure prediction, not protein folding
Isn't the folding how the structure is created?
Re: Chemistry Nobel: Computational protein design and protein structure prediction
#339Earlier quoted context omitted.
> tried to go back and ask to do a PhD in, say, Physics - I'd be promptly told to go fuck myself Only if you need money. If you pay the tuition they'll receive you with open arms. I've seen this for a guy is his mid to late 30s. As everything in the states, it's completely pay to play and largely pay to win.
What? Physics programs don't work like that, at least not T1-2 ones I know about. A physics PhD is not pay to play and anyone thinking it is would fail out on their qual at every university I'm familiar with.
> and anyone thinking it is would fail out on their qual
That I don't know but I have my doubts.
This was in a very well know university, so make of it what you wish.
I won't give any further details.
Re: Chemistry Nobel: Computational protein design and protein structure prediction
#340Earlier quoted context omitted.
There were at least hundreds of thousands if not millions who had easier starts them Jeff Besos.
The mental exercise is to compare two identical Jeff Bezos' (identify his attributes), one has the background/funds they did, one doesn't. Of course, that's not possible, so then you do the same with other highly intelligent and skilled tech professionals. I'd argue that without the funding and other resources, those skilled pro's won't get anywhere. But with it, some would do incredibly well. It's not common in a gl…
I think the question is not whether Bezos, or Gates, were helped by a reasonably wealthy family. The question is- was that wealth helpful because it allowed them to fully develop their own potential; or they have no merit at all and anybody with that wealth would have done the same?
I think those who point out the privileged start of these entrepreneurs are suggesting the second, and yet that makes no sense (millions had the same privilege and didn't get anywhere close).