Differential sensing with arrays of de novo designed peptide assemblies

DOI: 10.1038/s41467-023-36024-y

Authors: William M. Dawson (University of Bristol) , Kathryn L. Shelley (University of Bristol) , Jordan M. Fletcher (University of Bristol; Rosa Biotech) , D. Arne Scott (University of Bristol; Rosa Biotech) , Lucia Lombardi (University of Bristol; Imperial College London) , Guto G. Rhys (University of Bristol; Cardiff University) , Tania J. Lagambina (Rosa Biotech) , Ulrike Obst (Rosa Biotech) , Antony J. Burton (University of Bristol; AstraZeneca) , Jessica A. Cross (University of Bristol) , George Davies (University of Bristol) , Freddie J. O. Martin (University of Bristol) , Francis J. Wiseman (University of Bristol) , R. Leo Brady (University of Bristol) , David Tew (GlaxoSmithKline (GSK)) , Christopher W. Wood (University of Bristol; University of Edinburgh) , Derek N. Woolfson (University of Bristol)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Nature Communications , VOL 14

State: Published (Approved)
Published: January 2023
Diamond Proposal Number(s): 12342 , 23269

Abstract: Differential sensing attempts to mimic the mammalian senses of smell and taste to identify analytes and complex mixtures. In place of hundreds of complex, membrane-bound G-protein coupled receptors, differential sensors employ arrays of small molecules. Here we show that arrays of computationally designed de novo peptides provide alternative synthetic receptors for differential sensing. We use self-assembling α-helical barrels (αHBs) with central channels that can be altered predictably to vary their sizes, shapes and chemistries. The channels accommodate environment-sensitive dyes that fluoresce upon binding. Challenging arrays of dye-loaded barrels with analytes causes differential fluorophore displacement. The resulting fluorimetric fingerprints are used to train machine-learning models that relate the patterns to the analytes. We show that this system discriminates between a range of biomolecules, drink, and diagnostically relevant biological samples. As αHBs are robust and chemically diverse, the system has potential to sense many analytes in various settings.

Journal Keywords: Assay systems; Biosensors; Fluorescent dyes; Protein design

Subject Areas: Biology and Bio-materials, Chemistry


Instruments: I02-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography

Added On: 29/01/2023 21:11

Documents:
s41467-023-36024-y.pdf

Discipline Tags:

Biochemistry Chemistry Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)