Rangefinder: A Semisynthetic FRET Sensor Design Algorithm

Joshua A. Mitchell, Jason H. Whitfield, William H. Zhang, Christian Henneberger, Harald Janovjak, Megan L. O'Mara, Colin J. Jackson

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)


Optical sensors based on the phenomenon of Förster resonance energy transfer (FRET) are powerful tools that have advanced the study of small molecules in biological systems. However, sensor construction is not trivial and often requires multiple rounds of engineering or an ability to screen large numbers of variants. A method that would allow the accurate rational design of FRET sensors would expedite the production of biologically useful sensors. Here, we present Rangefinder, a computational algorithm that allows rapid in silico screening of dye attachment sites in a ligand-binding protein for the conjugation of a dye molecule to act as a Förster acceptor for a fused fluorescent protein. We present three ratiometric fluorescent sensors designed with Rangefinder, including a maltose sensor with a dynamic range of >300% and the first sensors for the most abundant sialic acid in human cells, N-acetylneuraminic acid. Provided a ligand-binding protein exists, it is our expectation that this model will facilitate the design of an optical sensor for any small molecule of interest.

Original languageEnglish
Pages (from-to)1286-1290
Number of pages5
JournalACS Sensors
Issue number11
Publication statusPublished - 23 Nov 2016
Externally publishedYes


  • arginine
  • biosensors
  • fluorescent dyes
  • FRET
  • maltose
  • Neu5Ac
  • periplasmic binding proteins
  • protein engineering
  • solute binding protein


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