{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ren J"],"funding":["G. Harold and Leila Y. Mathers Charitable Foundation","HHS | National Institutes of Health","U.S. Department of Energy","Howard Hughes Medical Institute","NIAID NIH HHS","Ludwig Institute for Cancer Research","NIGMS NIH HHS"],"pagination":["e2117401119"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8944926"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["119(12)"],"pubmed_abstract":["Affinity maturation of protein–protein interactions is an important approach in the development of therapeutic proteins such as cytokines. Typical experimental strategies involve targeting the cytokine-receptor interface with combinatorial libraries and then selecting for higher-affinity variants. Mutations to the binding scaffold are usually not considered main drivers for improved affinity. Here we demonstrate that computational design can provide affinity-enhanced variants of interleukin-2 (IL-2) “out of the box” without any requirement for interface engineering. Using a strategy of global IL-2 structural stabilization targeting metastable regions of the three-dimensional structure, rather than the receptor binding interfaces, we computationally designed thermostable IL-2 variants with "],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pubmed_title":["Interleukin-2 superkines by computational design."],"pmcid":["PMC8944926"],"funding_grant_id":["n/a","R37 AI051321","P30 GM133894","R01 AI051321","SciDAC","NIH-RO1-AI51321","MF-1802-00128"],"pubmed_authors":["Picton LK","Garcia KC","Jude KM","Ren J","Chu AE","Huang PS","Montano Romero A","Su L","Kare AJ"],"additional_accession":[]},"is_claimable":false,"name":"Interleukin-2 superkines by computational design.","description":"Affinity maturation of protein–protein interactions is an important approach in the development of therapeutic proteins such as cytokines. Typical experimental strategies involve targeting the cytokine-receptor interface with combinatorial libraries and then selecting for higher-affinity variants. Mutations to the binding scaffold are usually not considered main drivers for improved affinity. Here we demonstrate that computational design can provide affinity-enhanced variants of interleukin-2 (IL-2) “out of the box” without any requirement for interface engineering. Using a strategy of global IL-2 structural stabilization targeting metastable regions of the three-dimensional structure, rather than the receptor binding interfaces, we computationally designed thermostable IL-2 variants with ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-05-30T18:48:12.222Z","creation":"2024-12-04T03:40:27.49Z"},"accession":"S-EPMC8944926","cross_references":{"pubmed":["35294290"],"doi":["10.1073/pnas.2117401119"]}}