The design of functional proteins using tensorized energy calculations.
Cell Rep Methods
; 3(8): 100560, 2023 08 28.
Article
de En
| MEDLINE
| ID: mdl-37671023
ABSTRACT
In protein design, the energy associated with a huge number of sequence-conformer perturbations has to be routinely estimated. Hence, enhancing the throughput and accuracy of these energy calculations can profoundly improve design success rates and enable tackling more complex design problems. In this work, we explore the possibility of tensorizing the energy calculations and apply them in a protein design framework. We use this framework to design enhanced proteins with anti-cancer and radio-tracing functions. Particularly, we designed multispecific binders against ligands of the epidermal growth factor receptor (EGFR), where the tested design could inhibit EGFR activity in vitro and in vivo. We also used this method to design high-affinity Cu2+ binders that were stable in serum and could be readily loaded with copper-64 radionuclide. The resulting molecules show superior functional properties for their respective applications and demonstrate the generalizable potential of the described protein design approach.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Radio-isotopes du cuivre
/
Récepteurs ErbB
Langue:
En
Journal:
Cell Rep Methods
Année:
2023
Type de document:
Article
Pays d'affiliation:
Allemagne