Accelerated Molecular Dynamics Applied to the Peptaibol Folding Problem.

Area of Science:

• Biophysics
• Computational Chemistry
• Structural Biology

Background:

• Enhanced sampling molecular dynamics simulations are emerging as powerful tools for studying protein folding.
• Accelerated molecular dynamics (aMD) enhances sampling by modifying the potential energy surface.
• Peptaibols, like Alamethicin F30/3, are amphipathic molecules with known membrane-perturbing activities.

Purpose of the Study:

• To investigate the folding dynamics of Alamethicin F30/3 using accelerated molecular dynamics (aMD) simulations.
• To elucidate the pathway from unfolded to near-native states for this peptaibol.
• To simulate the Alamethicin F30/3 hexamer channel in a membrane environment.

Main Methods:

• Utilized accelerated molecular dynamics (aMD) simulations to study protein folding.
• Performed three consecutive simulations of approximately 900 ns each.
• Simulated the Alamethicin F30/3 hexamer channel in an E. coli mimicking membrane under an external electric field.

Main Results:

• Observed N-terminal folding within the first 100 ns and C-terminal folding around 800 ns.
• Achieved near-native conformation in approximately 1 μs using a stronger potential boost.
• Simulated channel formation correlated with experimental findings.

Conclusions:

• aMD simulations are effective for determining peptaibol structures.
• aMD simulations provide insights into the folding dynamics of peptaibols.
• This approach accelerates the study of protein folding compared to classical molecular dynamics.