We succeeded in solving crystal structures of five of the binder-target complexes, and all five are very close to the corresponding computational design models. Experimental data on nearly half a million computational designs and hundreds of thousands of point mutants provide detailed feedback on the...
The design of proteins that bind to a specific site on the surface of a target protein using no information other than the three-dimensional structure of the target remains a challenge1–5. Here we describe a general solution to this problem that starts
Recently it has become possible to de novo design high affinity protein binding proteins from target structural information alone. There is, however, considerable room for improvement as the overall design success rate is low. Here, we explore the augmen
Design of protein-binding proteins from the target structure alone Longxing Cao, Brian Coventry, Inna Goreshnik, Buwei Huang, William Sheffler, Joon Sung Park, Kevin M. Jude, Iva Marković, Rameshwar U. Kadam, Koen H. G. Verschueren, Kenneth Verstraete, Scott Thomas Russell Walsh, Nathaniel...
4 | Using PocketGen to design protein pockets for binding with important ligands. a–c, Illustrations of protein–ligand interaction analysis for three target molecules (HCY (a), APX (b) and 7V7 (c)). PocketGen refers to the protein pocket designed by PocketGen, and Original denotes the ...
1.4 Binder design Improving de novo Protein Binder Design with Deep Learning Nathaniel Bennett, Brian Coventry, Inna Goreshnik, Buwei Huang, Aza Allen, Dionne Vafeados, Ying Po Peng, Justas Dauparas, Minkyung Baek, Lance Stewart, Frank DiMaio, Steven De Munck, Savvas Savvi...
First, drugs can be designed to bind regions of viral proteins that are less prone to mutations or target human proteins that interact with viral ones. Importantly, such options are not available in the case of enzyme inhibitor design. Second, antiviral therapy can be constructed in a way ...
In the publication by Yang et al., yeast surface display yielded a protein binder based on a fibronectin scaffold, which is able to reversibly neutralize the membranolytic activity of PFO. This binder was engineered to bind and inhibit PFO at neutral pH, but to release PFO in the acidic ...
The idea of designer isopeptide bonds within a protein, and better still, between a native target protein and a de novo binder is cool, but rather unfeasible as the risks for failure are high, other technologies could conceivably achieve somewhat similar results, and there are too many technical...
Changes in aggregation can also be coupled to and used to control downstream cellular processes. One example of this capability was demonstrated in the design of the yTRAP (yeastTranscriptionalReporting ofAggregatingProtein) system, a genetic tool we developed for high-throughput sensing and control ...