3 ms·
"We don't know too much about the exact model they made but it looks sufficiently generalizable to be able to give a candidate protein structure for any given s
by timr 6y ago
"We don't know too much about the exact model they made but it looks sufficiently generalizable to be able to give a candidate protein structure for any given sequence. It doesn't automatically cure cancer and inject the drug but that by itself is an amazing tool that if available to everyone will revolutionize biology experimentation."
They say on their own press-release page that side-chains are a future research problem, and nothing about their method description makes me believe they've innovated on all-atom modeling. This software seems able to generate good models of protein backbones; these kinds of models certainly have uses, but a backbone model is not enough for drug design.
This is certainly an advancement, but you're exaggerating the scope of the accomplishment.
" I only feel pity for the graduate students still trying to crystallize proteins in this day and age."
Nothing about this changes the fact that protein crystallography is a gold-standard method for determining a protein structure. CryoEM has made it possible to obtain good structures for classes of proteins we could never achieve before, and it's certainly interesting if we can run a computer for a few days to get a 1Å ab initio model for a protein sequence, but we could already do that for a large class of proteins with homology modeling. These predicted structures still aren't generally that useful for drug design, where tiny details of molecular interactions matter.
To put it in perspective: protein energetics are measured on the scale of tens of kcal / mol. Protein-drug interactions are measured in fractions of a kcal. A single hydrogen bond or cation-pi interaction or displaced water molecule can make the difference between a drug candidate and an abandoned lead. Tiny changes in backbone position make the difference between a good structure and a bad one. Alphafold isn't doing that kind of modeling.
- ramraj07 6y agoOf course, they havent solved everything, but you seem to be doing exactly what I accuse that entire field (and academia in general) of doing - which is to insist a problem is intractable or hard and undermine someone potentially challenging that. When they released the 2018 results tbey field did embrace it (for sure I'd consider the groups organizing CASP as at least forward thinking) but was still skeptical on how much more progress it can make; now they blow everyone's minds again by a monumental leap and again people want to come say of course this is the last big jump! I understand the self preservation instincts that kick in when there's a suggestion that the entire field has been in a dark age for a while, but I hope you can see that there might be something fundamentally wrong with how research is done in academia and that is to blame for why this didn't happen sooner, and why it's so hard for many to embrace it. Regarding your comments on the inapplicability of this current solution for docking, I'm sure that's the next project they're taking up, and let's see where that goes. This is exactly the same type of progression that happened with Go, where when their software bet a professional player everyone's like "yeah but I bet he wasn't that good". A few years later and Lee Sedol just decided to retire. I am interested to see what happens to that entire academic field in a similar vein, though my interests are more in knowing how science can advance from more people thinking this way.
- deeviant 6y ago> Nothing about this changes the fact that protein crystallography is a gold-standard method for determining a protein structure. Yes it does. Protein crystallography is/was the gold-standard. Once this result is verified and accepted by the scientific community as a whole, that changes.
- deleted 6y ago[deleted]
- blinding-streak 6y agoAre you always so dismissive of Nobel-level achievements?