Advancing Peptide-Based Biorecognition Elements for Biosensors Using In-Silico Evolution

Sensors for human health and performance monitoring require biological recognition elements (BREs) at device interfaces for the detection of key molecular biomarkers that are measurable biological state indicators. BREs, including peptides, antibodies, and nucleic acids, bind to biomarkers in the vicinity of the sensor surface to create a signal proportional to the biomarker concentration. The discovery of BREs with the required sensitivity and selectivity to bind biomarkers at low concentrations remains a fundamental challenge. In this study, we describe an in-silico approach to evolve higher sensitivity peptide-based BREs for the detection of cardiac event marker protein troponin I (cTnI) from a previously identified BRE as the parental affinity peptide. The P2 affinity peptide, evolved using our in-silico method, was found to have ∼16-fold higher affinity compared to the parent BRE and ∼10 fM (0.23 pg/mL) limit of detection. The approach described here can be applied towards designing BREs for other biomarkers for human health monitoring.

Publication year: 2018
Authors: Xiao X. 1, Kuang Z. 2, Slocik J.M. 2, Tadepalli S. 4, Brothers M. 3, Kim S. 3, Mirau P.A. 2, Butkus C. 2, Farmer B.L. 2, Singamaneni S. 4, Hall C.K. 1, Naik R.R. 3
Affiliations:
1 – Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, North Carolina 27695, United States
2 – Materials and Manufacturing Directorate and 3 – 711th Human Performance Wing, Air Force Research Laboratory, Wright-Patterson Air Force Base, Dayton, Ohio 45433, United States
4 – Department of Mechanical Engineering and Materials Science, Institute of Materials Science and Engineering, Washington University in St. Louis, St. Louis, Missouri 63130, United States
Published in: ACS Sensors, 2018, Vol. 3, Issue 5, p. 1024–1031
DOI: 10.1021/acssensors.8b00159

MP-SPR KEYWORDS

biosensor cardiac event marker computational modelling fragments in silico peptide-protein interaction troponin binding affinity and kinetics troponin binding peptides
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