> Building better models that simulate a human biological process must have some sort of payoff? It increases human knowledge, and should provide a foundation on which others can build.
That really is still not clear for the models described in the article. In reality, these models are rehashes of what Murcko was having people do 25 years ago. Big articles were written about Vertex applying Free Energy Perturbation with pictures of Murcko accompanied by David Pearlman and Govinda Bhisetti. A book was written about these efforts, The Billion-Dollar Molecule, and more recently a sequel which partially describes how Vertex's efforts using these methods failed (The Antidote).
Obviously, computational power has improved by orders of magnitude since 1989. So have our parameters for modeling proteins and small molecules. But it really is still not clear that MD or FEP really provide any useful insights into proteins that cannot be obtained more simply via NMR-based screens and linear regression. In fact, I recently saw a talk by Relay's VP of Computation where he described using Free Wilson Analysis at Relay[1] for their drug discovery, which is a linear regression method from 1964...
Great context. You don't have to go too far back in the archives of this site to find discussion on Andy Grove's similar big project to use in silico to destroy traditional pharma discovery. We haven't heard much from that project since.
That really is still not clear for the models described in the article. In reality, these models are rehashes of what Murcko was having people do 25 years ago. Big articles were written about Vertex applying Free Energy Perturbation with pictures of Murcko accompanied by David Pearlman and Govinda Bhisetti. A book was written about these efforts, The Billion-Dollar Molecule, and more recently a sequel which partially describes how Vertex's efforts using these methods failed (The Antidote).
Obviously, computational power has improved by orders of magnitude since 1989. So have our parameters for modeling proteins and small molecules. But it really is still not clear that MD or FEP really provide any useful insights into proteins that cannot be obtained more simply via NMR-based screens and linear regression. In fact, I recently saw a talk by Relay's VP of Computation where he described using Free Wilson Analysis at Relay[1] for their drug discovery, which is a linear regression method from 1964...
[1] https://github.com/PatWalters/Free-Wilson