Improving Protein Expression, Stability, and Function with ProteinMPNN
University of Washington · CIC bioGUNE · +3 more institutions
Abstract
Natural proteins are highly optimized for function but are often difficult to produce at a scale suitable for biotechnological applications due to poor expression in heterologous systems, limited solubility, and sensitivity to temperature. Thus, a general method that improves the physical properties of native proteins while maintaining function could have wide utility for protein-based technologies. Here, we show that the deep neural network ProteinMPNN, together with evolutionary and structural information, provides a route to increasing protein expression, stability, and function. For both myoglobin and tobacco etch virus (TEV) protease, we generated designs with improved expression, elevated melting…
Citation impact
- FWCI
- 60.21
- Percentile
- 100%
- References
- 40
Authors
16Topics & keywords
- Chemistry
- Protein expression
- Myoglobin
- Function (biology)
- Protease
- Protein stability
- Computational biology
- Heterologous expression
- Good health and well-being
Funding
- SFSchmidt Futures
- NSNational Science FoundationAwards: HDTRA1-19-1-0003, 1629214, DE-AC02-05CH11231, CHE-1629214
- HHHoward Hughes Medical Institute
- UDU.S. Department of EnergyAwards: -AC02-05CH11231, DE-AC02- 05CH11231, 05CH11231, AC02-05CH11231, DE-AC02, DE-AC02-05CH11231, DE-AC02-
- BABill and Melinda Gates FoundationAward: OPP1156262
- APAlfred P. Sloan FoundationAward: G-2021-16899
- WRWashington Research Foundation
- EMEuropean Molecular Biology OrganizationAwards: ALTF 139-2018, ALTF 1047-2019
- UOUniversity of Washington
- OPOpen Philanthropy Project
- HFHuman Frontier Science ProgramAwards: LT000838/2018-C, LT000395/2020-C
- IBIkerbasque, Basque Foundation for ScienceAward: PID2021-125946OB-I00
- NINational Institutes of HealthAward: R35 GM124773
- DADefense Advanced Research Projects AgencyAwards: HR0011-21-2-0012, DE-AC02-05CH11231
- DTDefense Threat Reduction AgencyAward: HDTRA1-19-1-0003
- ARAdvanced Research Projects Agency - EnergyAward: 2459-1671
- OOOffice of ScienceAwards: AC02-05CH11231, -AC02-05CH11231, DE-AC02
- AEAgencia Estatal de InvestigaciónAwards: CEX2021-001136-S, PID2021-125946OB-I00
- NINational Institute of Allergy and Infectious DiseasesAward: R0AI160052
- DODivision of ChemistryAwards: CHE-1629214, 1629214, DE-AC02-05CH11231
- DODivision of Biological InfrastructureAward: DBI 1937533
- BEBasic Energy SciencesAwards: DE-AC02, AC02-05CH11231, DE-AC02-05CH11231, -AC02-05CH11231
- AFAir Force Office of Scientific Research