3 ms·

Explaining why this won’t happen is the obvious follow up question. When is “improved structure prediction” useful or important? Often a process is simplified

Explaining why this won’t happen is the obvious follow up question. When is “improved structure prediction” useful or important? Often a process is simplified or distilled down to a sound bite for the general population. Then we simply repeat without understanding the details.

dekhn 4y ago
Improved structure prediction is mainly useful in hypothesis generation when doing hypothesis-driven science (IE, you want to confirm that a specific part of a protein plays a functional role in a disease). Its also a nice way to think creatively about your protein of interest. THe problem is those distilled soundbites get learned by the next generation and they try to apply it. At least I will give AlphaFold/DM credit for correcting their language - originally they claimed AF solved protein folding, but really, it's just a structure predictor, which is an entirely different area. Unfortunately, people basically taught computer scientists that the Anfinsen Dogma was truth. I fell for this for many years.
- warinukraine 4y ago
  https://en.wikipedia.org/wiki/Anfinsen%27s_dogma https://en.wikipedia.org/wiki/Anfinsen%27s_dogma > It states that, at least for a small globular protein in its standard physiological environment, the native structure is determined only by the protein's amino acid sequence. Seems like "no true scotsman". If you present a counter example, they'll go "but this is only true for "small", the one you gave me isn't small.
  - dekhn 4y ago
    Let's say you have a pool of smart first year grad students you want to inspire to work hard on problems for you for the next 7 years. Do you say "we're going to give you a problem that is unsolved but likely has a general solution, and you have a chance of making progress, publishing, and moving on to a postdoc" or do you say "THis is an impossibly hard problem and you will only make a marginal improvement on the state of the art because the problem space is so complex and large"? You say the first because it gets the students interested and working on the problem, only to learn many years later that the simplified model presented was so simplified it wasn't helpful. I fell for that and spent years working on drug discovery, structure prediction, etc, only to realize: while what Anfinsen said was true, it only applies to about 1% of protein space. It's not so much a "no true scotsman" as "some scotsmen wear quilts, and others have beards, but neither of those is sufficient to classify an example as scots".

dekhn 4y ago

Improved structure prediction is mainly useful in hypothesis generation when doing hypothesis-driven science (IE, you want to confirm that a specific part of a protein plays a functional role in a disease). Its also a nice way to think creatively about your protein of interest. THe problem is those distilled soundbites get learned by the next generation and they try to apply it. At least I will give AlphaFold/DM credit for correcting their language - originally they claimed AF solved protein folding, but really, it's just a structure predictor, which is an entirely different area. Unfortunately, people basically taught computer scientists that the Anfinsen Dogma was truth. I fell for this for many years.

warinukraine 4y ago
https://en.wikipedia.org/wiki/Anfinsen%27s_dogma https://en.wikipedia.org/wiki/Anfinsen%27s_dogma > It states that, at least for a small globular protein in its standard physiological environment, the native structure is determined only by the protein's amino acid sequence. Seems like "no true scotsman". If you present a counter example, they'll go "but this is only true for "small", the one you gave me isn't small.
- dekhn 4y ago
  Let's say you have a pool of smart first year grad students you want to inspire to work hard on problems for you for the next 7 years. Do you say "we're going to give you a problem that is unsolved but likely has a general solution, and you have a chance of making progress, publishing, and moving on to a postdoc" or do you say "THis is an impossibly hard problem and you will only make a marginal improvement on the state of the art because the problem space is so complex and large"? You say the first because it gets the students interested and working on the problem, only to learn many years later that the simplified model presented was so simplified it wasn't helpful. I fell for that and spent years working on drug discovery, structure prediction, etc, only to realize: while what Anfinsen said was true, it only applies to about 1% of protein space. It's not so much a "no true scotsman" as "some scotsmen wear quilts, and others have beards, but neither of those is sufficient to classify an example as scots".