2026-09-19T21:11:55Zhttps://dspace.mit.edu/server/oai/requestoai:dspace.mit.edu:1721.1/1428392022-06-01T03:02:17Zcom_1721.1_7582com_1721.1_7581col_1721.1_131023
Jacobson, Joseph M.
Tripathy, Soumya Pratap
Program in Media Arts and Sciences (Massachusetts Institute of Technology)
2022-05-31T13:31:58Z
2022-05-31T13:31:58Z
2021-09
2022-05-25T15:55:52.438Z
https://hdl.handle.net/1721.1/142839
https://orcid.org/0000-0001-5778-4430
The novel coronavirus SARS-CoV-2 continues to pose a significant global health threat. Along with vaccines and targeted therapeutics, there is a critical need for rapid diagnostic solutions. In this work, we employ a deep learning-based protein design to engineer molecular beacons that function as conformational switches for high sensitivity detection of the SARS-CoV-2 spike protein receptor-binding domain (SRBD). The beacons contain two peptides, together forming a heterodimer, and a binding ligand between them to detect the presence of S-RBD. In the absence of S-RBD (OFF), the peptide beacons adopt a closed conformation that opens when bound to the S-RBD and produces a fluorescence signal (ON), utilizing a fluorophore-quencher pair at the two ends of the heterodimer stems. Two candidate beacons, C17LC21, and C21LC21 can detect the S-RBD with limits of detection (LoD) in the sub-picomolar range. We envision that these beacons can be easily integrated with on-chip optical sensors to construct a point-of-care diagnostic platform for SARS-CoV-2.
S.M.
Massachusetts Institute of Technology
In Copyright - Educational Use Permitted
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http://rightsstatements.org/page/InC-EDU/1.0/
Sub-Picomolar Detection of SARS-CoV-2 RBD via Computationally-Optimized Peptide Beacons
Thesis
application/pdf
Master
Master of Science in Media Arts and Sciences
Publication
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unknown
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<Abstract>The novel coronavirus SARS-CoV-2 continues to pose a significant global health threat. Along with vaccines and targeted therapeutics, there is a critical need for rapid diagnostic solutions. In this work, we employ a deep learning-based protein design to engineer molecular beacons that function as conformational switches for high sensitivity detection of the SARS-CoV-2 spike protein receptor-binding domain (SRBD). The beacons contain two peptides, together forming a heterodimer, and a binding ligand between them to detect the presence of S-RBD. In the absence of S-RBD (OFF), the peptide beacons adopt a closed conformation that opens when bound to the S-RBD and produces a fluorescence signal (ON), utilizing a fluorophore-quencher pair at the two ends of the heterodimer stems. Two candidate beacons, C17LC21, and C21LC21 can detect the S-RBD with limits of detection (LoD) in the sub-picomolar range. We envision that these beacons can be easily integrated with on-chip optical sensors to construct a point-of-care diagnostic platform for SARS-CoV-2.</Abstract>
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