Imaging alpha-hemolysin with molecular dynamics: ionic conductance, osmotic permeability, and the electrostatic potential map.

alpha-Hemolysin of Staphylococcus aureus is a self-assembling toxin that forms a water-filled transmembrane channel upon oligomerization in a lipid membrane. Apart from being one of the best-studied toxins of bacterial origin, alpha-hemolysin is the principal component in several biotechnological applications, including systems for controlled delivery of small solutes across lipid membranes, stochastic sensors for small solutes, and an alternative to conventional technology for DNA sequencing. Through large-scale molecular dynamics simulations, we studied the permeability of the alpha-hemolysin/lipid bilayer complex for water and ions.

Microscopic Kinetics of DNA Translocation through synthetic nanopores.

We have previously demonstrated that a nanometer-diameter pore in a nanometer-thick metal-oxide-semiconductor-compatible membrane can be used as a molecular sensor for detecting DNA. The prospects for using this type of device for sequencing DNA are avidly being pursued. The key attribute of the sensor is the electric field-induced (voltage-driven) translocation of the DNA molecule in an electrolytic solution across the membrane through the nanopore.

Sizing DNA using a nanometer-diameter pore.

Each species from bacteria to human has a distinct genetic fingerprint. Therefore, a mechanism that detects a single molecule of DNA represents the ultimate analytical tool. As a first step in the development of such a tool, we have explored using a nanometer-diameter pore, sputtered in a nanometer-thick inorganic membrane with a tightly focused electron beam, as a transducer that detects single molecules of DNA and produces an electrical signature of the structure.

Insights into the molecular mechanism of rotation in the Fo sector of ATP synthase.

F(1)F(o)-ATP synthase is a ubiquitous membrane protein complex that efficiently converts a cell's transmembrane proton gradient into chemical energy stored as ATP. The protein is made of two molecular motors, F(o) and F(1), which are coupled by a central stalk. The membrane unit, F(o), converts the transmembrane electrochemical potential into mechanical rotation of a rotor in F(o) and the physically connected central stalk.