ELECTRON TRANSFER RATE BASED DETECTION OF LIGANDS

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Long-range electron transfer rates are exquisitely sensitive to donor-acceptor geometry and the conformation and motions of the intervening medium. The rate of electron transfer through proteins may thus potentially serve as a very sensitive probe of ligand- induced changes in protein structure and dynamics. Recently developed combinatorial techniques provide an ability to design proteins that bind to any given target molecule, suggesting that a method of electronically detecting ligand-induced conformational changes might provide a general means of monitoring the presence of any specific substrate. We propose here experiments aimed at monitoring the ligand-induced folding of Hin-recombinase via changes in through-protein electron transfer rate. These will demonstrate the feasibility of a general, electron-transfer based electronic technique for the detection of specific ligands of medicinal significance.