Current Rectification and Ionic Selectivity of α-Hemolysin: Coarse-Grained Molecular Dynamics Simulations.

Area of Science:

• Biophysics
• Computational Biology
• Nanotechnology

Background:

• Understanding molecular-level physical processes in nanopore experiments requires detailed microscopic information.
• Coarse-grained (CG) models offer a computationally efficient alternative to all-atom simulations for studying complex biological systems.

Purpose of the Study:

• To investigate ionic transport through the alpha-hemolysin (α-HL) protein nanopore using molecular dynamics (MD).
• To identify the roles of charged amino acids in determining nanopore ionic current characteristics.

Main Methods:

• Performed 1.5 μs coarse-grained molecular dynamics simulations using the MARTINI force field and polarizable water.
• Simulated ionic transport through the α-HL nanopore embedded in a lipid bilayer under various applied electric fields.
• Neutralized charged amino acids in 12 different systems and ran approximately 100 simulations with electric fields ranging from ±0.04 V/nm.

Main Results:

• Observed characteristic nanopore behaviors, including current asymmetry and anion selectivity, consistent with experimental data.
• Identified specific charged amino acids within the α-HL pore that influence ionic current properties.
• Generated ionic density maps to provide microscopic explanations for the observed ionic current features.

Conclusions:

• Validated the coarse-grain approach for accurately studying ionic transport through protein nanopores.
• Provided a molecular-level understanding of the mechanisms underlying current asymmetry and ion selectivity in the α-HL nanopore.
• Demonstrated the utility of CG-MD simulations in complementing experimental findings in nanopore science.