Most docking and cofolding methods assume the protein pocket is roughly fixed: place the ligand into a shape that's already there. That assumption breaks on a lot of real targets, and EV-A71 2A protease is a clear example. When a ligand binds, a loop next to the site moves about 4 Å. Every one of the 802 structures in OpenBind's benchmark needs that rearrangement, which is why classical docking into the unbound structure has only 5% success rate. Turns out, the real problem isn't "where does the ligand needs to go" it's "what shape does the protein become when this specific ligand shows up." Ligand and protein are coupled, and you have to solve them together. Pearl predicts that motion from sequence and the ligand alone. On one compound that no other zero-shot method in the benchmark solves, it placed the ligand within 0.28 Å of the crystal structure and got the loop rearrangement right. Modeling induced fit instead of assuming a rigid pocket is a big part of why this holds up on actual programs.