Interleukin-2 superkines by computational design
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- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, HHMI, Stanford University School of Medicine, Stanford, CA 94305
- Department of Bioengineering, Stanford University, Stanford, CA 94305, Biophysics Program, Stanford University, Stanford, CA 94305
- Department of Bioengineering, Stanford University, Stanford, CA 94305
- Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, HHMI, Stanford University School of Medicine, Stanford, CA 94305, Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305
Significance While computational engineering of therapeutic proteins is a desirable goal, in practice the optimization of protein–protein interactions requires substantial experimental intervention. We present here a computational approach that focuses on stabilizing core protein structures rather than engineering the protein–protein interface. Using this approach, we designed thermostabilized interleukin-2 (IL-2) variants that bind tightly to their receptor without experimental optimization, mimicking the properties of the yeast-display engineered IL-2 variant “super-2.” Our results suggest that structure-guided stabilization may be a general method for in silico affinity maturation of protein–protein interactions.
- Research Organization:
- SLAC National Accelerator Laboratory (SLAC), Menlo Park, CA (United States)
- Sponsoring Organization:
- National Institutes of Health (NIH); USDOE; USDOE Office of Science (SC), Advanced Scientific Computing Research (ASCR). Scientific Discovery through Advanced Computing (SciDAC); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities Division. Argonne National Laboratory (ANL)
- Grant/Contract Number:
- AC02-06CH11357; AC02-76SF00515
- OSTI ID:
- 1855289
- Journal Information:
- Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 12 Vol. 119; ISSN 0027-8424
- Publisher:
- Proceedings of the National Academy of SciencesCopyright Statement
- Country of Publication:
- United States
- Language:
- English
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