Introducing an artificial photo-switch into a biological pore: A model study of an engineered α-hemolysin.

Balasubramanian Chandramouli, Danilo Di Maio, Giordano Mancini, Giuseppe Brancato

Biochimica et biophysica acta 2016 Apr

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In recent years, engineered biological pores responsive to external stimuli have been fruitfully used for various biotechnological applications. Moreover, the strategy of tethering photo-switchable moieties into biomolecules has provided an unprecedented temporal control of purposely designed nanodevices, as demonstrated, for example, by the light-mediated regulation of the activity of enzymes and biochannels. Inspired by these advancements, we propose here a de novo designed nanodevice featuring the α-hemolysin (αHL) membrane channel purposely functionalized by an artificial "on/off" molecular switch. The switch, which is based on the photo-isomerization of the azobenzene moiety, introduces a smart nano-valve into the natural non-gated pore to confer tunable transport properties. We validated through molecular dynamics simulations and free energy calculations the effective inter-conversion of the engineered αHL pore between two configurations corresponding to an "open" and a "closed" form. The reported switchable translocation of a single-stranded DNA fragment under applied voltage supports the promising capabilities of this nanopore prototype in view of molecular sensing, detection and delivery applications at single-molecule level. Copyright © 2016 Elsevier B.V. All rights reserved

Citation

Balasubramanian Chandramouli, Danilo Di Maio, Giordano Mancini, Giuseppe Brancato. Introducing an artificial photo-switch into a biological pore: A model study of an engineered α-hemolysin. Biochimica et biophysica acta. 2016 Apr;1858(4):689-97