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Comment by andbberger | Hacker News Reader

This comes across as exceptionally naive. Protein-engineering is a fundamental technology, and we've been constrained computationally for decades. Few things would have as far-reaching an impact on society as being able to accurately predict protein structure would.

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You can call me naive, or you can read my papers. For example, https://www.nature.com/articles/nchem.1821 is a massive simulation of a GPCR that my team designed and ran. It's a similar idea to the Relay work (simulate the dynamics of the protein, make a markov model of the subsets with transition parameters) With that tech, we could easily implement computational mutagenesis. I agree 100% that protein engineering is a great technology and I wish we could do it rationally. But to be honest, none of my computational work can beat what Jim Wells did at Genentech in the late 90s (converting subtilisin to subtiligase through amino acid mutations).

Here's another paper I wrote, https://www.ncbi.nlm.nih.gov/pubmed/24265211 which demonstrates there was a systematic error in protein force field implementations; our work was a major breakthrough in improving structure prediction.

Also, being able to predict structures isn't sufficient to engineer protein function.

Please don't call people naive; especially if they are experts in their field.

I'm confused as to why you're addressing this commenter using "argument from authority" when you seem to be weakening your position, suggesting that studying protein dynamics has led to significant advances in the field. It doesn't change the fact that you made a flippant remark that a team of some of the most experienced drug discovery scientists in the industry are wasting their time using this approach (despite not having worked in drug discovery, i.e. not an expert in the field), instead of just explaining why you believe this. Didn't mean to make it personal, that's just how I interpret your comment.

There have been plenty of amazing discoveries and advances in the area of protein Dynamics. but I don't think that anybody has any authority to claim that this particular approach is going to revolutionize pharmaceutical discovery.

If you'd like I can also show you a few of my drug Discovery papers. I'm actually one of Shaw's biggest competitors in the field and advise Venture Capital companies who consider investing in companies like relay

Relay is not doing protein engineering or working on predicting protein structure. They are making models of protein dynamics to assist in drug discovery (often using already determined structures). We both disagree with the parent commenter that it's a waste, and to claim that Murcko and D.E. Shaw are going in "blindly" would be ignoring decades of research on protein dynamics of some of the hardest drug targets out there. The fact remains that there aren't many success stories of using simulations of protein dynamics to accelerate drug discovery. Computational chemistry protocols used routinely in pharma drug discovery typically do not include this type of detail.

I know, just an example.

I wouldn't bet against relay right now - historical precendent is irrelevant here. There's an enormous opportunity for application of ML techniques in protein engineering (as an umbrella term...) - I've really been itching to take a crack at it but it's a moonshot...

A well-positioned player with the right people could make a killing in this market right now.

Can you describe just how they would make a killing? I mean, in terms of making a product that sold, and produced drugs of value.

Sure. My rates for consulting start at $500/hr...

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