Designing Hydrophobic Gates into Biomimetic Nanopores

Abstract

The use of nanopores is fast being a major scientific tool in molecular analysis and detection due to their ability to detect polynucleotides, proteins and small molecules. Biomimetic modelling of pores allows for a specific function to be incorporated into the molecular structure of the nanopore, based on amino acid motifs found in existing protein structures.An initial beta barrel model was built computationally, based on the transmembrane domain of 14 stranded beta-barrel pore, alpha-hemolysin. Hydrophobic and hydrophilic residues were built in a specific arrangement within the structure to replicate an hourglass shape cavity with a central constriction. From this, pore conductions were observed via Molecular Dynamics (MD) and selected models were transformed into hybrid pores in which the location of hydrophobic residues differed to give constricting regions surrounded by hydrophilic residues. From All Atom MD simulations, a hydrophobic gating mechanism has been established within these toy models with intermittent water currents through the pore giving an insight into possible biomimetic motifs which could be biochemically integrated into the wild type protein.