Cyclic peptide structure prediction and design using AlphaFold2
University of Washington · Massachusetts Institute of Technology · +2 more institutions
Abstract
Small cyclic peptides have gained significant traction as a therapeutic modality; however, the development of deep learning methods for accurately designing such peptides has been slow, mostly due to the lack of sufficiently large training sets. Here, we introduce AfCycDesign, a deep learning approach for accurate structure prediction, sequence redesign, and de novo hallucination of cyclic peptides. Using AfCycDesign, we identified over 10,000 structurally-diverse designs predicted to fold into the designed structures with high confidence. X-ray crystal structures for eight tested de novo designed sequences match very closely with the design models (RMSD
Citation impact
- FWCI
- 31.60
- Percentile
- 100%
- References
- 57
Authors
17Topics & keywords
- Peptide
- Computational biology
- Computer science
- Biology
- Biochemistry
- Zero hunger
Funding
- NSNational Science FoundationAwards: P30GM133893, P30 GM124165, MCB2032259, DE-AC02-06CH11357, DE-SC0012704
- HHHoward Hughes Medical Institute
- UDU.S. Department of EnergyAwards: AC02-06CH11357, KP1607011, P30 GM124165, SC0012704, P30GM133893, DE-AC02, 06CH11357, DE-AC02-06CH11357, DE-AC02-
- BABill and Melinda Gates FoundationAward: OPP1156262
- AAmgen
- UOUniversity of WashingtonAward: DE-AC02-06CH11357
- ECEuropean CommissionAwards: 101059124, DE-AC02-06CH11357
- NINational Institutes of HealthAwards: P30 GM124165, P30GM133893, DE-AC02-06CH11357, GM124165, OPP1156262, DP5OD026389
- DADefense Advanced Research Projects AgencyAwards: HR0011-21-2-0012, HR001120S0052, DE-SC0012704
- DTDefense Threat Reduction AgencyAward: GRANT13030960
- OOOffice of ScienceAwards: DE-AC02-06CH11357, DE-AC02, 06CH11357, SC0012704, AC02-06CH11357, KP1607011, DE-SC0012704
- HEHORIZON EUROPE Framework Programme
- NINational Institute of General Medical SciencesAwards: P30GM133893, DE-AC02-06CH11357, P30 GM124165, GM124165
- BABiological and Environmental ResearchAwards: DE-SC0012704, DE-AC02-06CH11357, P30 GM124165, KP1607011
- ANArgonne National LaboratoryAwards: DE-AC02, DE-SC0012704, 06CH11357, P30 GM124165, AC02-06CH11357
- BNBrookhaven National LaboratoryAwards: P30 GM124165, SC0012704, DE-AC02-06CH11357