De novo design of small molecule–regulated protein oligomers
Fudan University · Westlake University · +1 more institution
Abstract
Small molecule-regulated protein oligomerization provides a powerful mechanism for manipulating biological processes by controlling protein proximity with high temporal precision. However, such systems only rarely exist in nature and remain a substantial challenge for de novo design. In this work, we describe a computational method for designing protein homooligomers whose assembly is regulated by small-molecule ligands with matching symmetry. We designed protein homotrimers regulated by the Food and Drug Administration (FDA)-approved drug amantadine and further designed amantadine-responsive heterodimers and heterotrimers. Biophysical characterization confirmed their amantadine-dependent assembly, and their…
Citation impact
- FWCI
- 45.66
- Percentile
- 100%
- References
- 75
Authors
9Topics & keywords
- Protein–protein interaction
- Mechanism (biology)
- Protein structure
- Synthetic biology
- Protein design
- Chemical biology
- Drug discovery
- Plasma protein binding
Funding
- NNNational Natural Science Foundation of ChinaAwards: 2020YFA0909200, 2021YFC2301401, 2022YFA1303700, 32370989
- MOMinistry of Science and Technology, Government of the People’s Republic of BangladeshAward: 2020YFA0909200
- NKNational Key Research and Development Program of ChinaAwards: 2021YFC2301401, 2022YFA1303700