"We demonstrate that our IsoDDE more than doubles the accuracy of AlphaFold 3 on a challenging protein-ligand structure prediction generalisation benchmark, predicts small molecule binding-affinities with accuracies that exceed gold-standard physics-based methods at a fraction of the time and cost, and is able to accurately identify novel binding pockets on target proteins using only the amino acid sequence as input."
It seems like a key challenge here is not just creating a protein that will bind to a specific site, but also ensuring that off-target binding won't happen. Is this feasible? I'm not familiar with this space, but RefSeq [1] shows 442M proteins and the human protein atlas seems to only cover 17.4k [2]. Do we have comprehensive knowledge of human proteins that would allow us to identify off-site affinities?
"We demonstrate that our IsoDDE more than doubles the accuracy of AlphaFold 3 on a challenging protein-ligand structure prediction generalisation benchmark, predicts small molecule binding-affinities with accuracies that exceed gold-standard physics-based methods at a fraction of the time and cost, and is able to accurately identify novel binding pockets on target proteins using only the amino acid sequence as input."
It seems like a key challenge here is not just creating a protein that will bind to a specific site, but also ensuring that off-target binding won't happen. Is this feasible? I'm not familiar with this space, but RefSeq [1] shows 442M proteins and the human protein atlas seems to only cover 17.4k [2]. Do we have comprehensive knowledge of human proteins that would allow us to identify off-site affinities?
[1] https://www.ncbi.nlm.nih.gov/refseq/
[2] https://www.proteinatlas.org/