Molecular simulation of protein dynamics in nanopores. II. Diffusion

Area of Science:

• Computational Biophysics
• Soft Matter Physics
• Nanotechnology

Background:

• Understanding protein transport through nanopores is crucial for applications like drug delivery and biosensing.
• Existing models often lack the resolution or simulation length to capture complex protein-pore interactions.
• The influence of protein size, temperature, and surface interactions on transport dynamics requires further investigation.

Purpose of the Study:

• To investigate the transport dynamics of single-domain alpha-helical proteins within nanopores.
• To analyze the effects of pore size, temperature, and protein-wall interactions (attractive vs. repulsive) on protein diffusivity.
• To develop a predictive framework for protein transport in nanopores.

Main Methods:

• Employed a novel combination of discontinuous molecular dynamics and the Langevin equation.
• Utilized an intermediate-resolution protein model for long simulations (several microseconds).
• Calculated protein diffusivity (D) under bulk conditions and as a function of protein length, temperature (T), pore size (h), and wall interaction potentials.

Main Results:

• Computed bulk diffusivities align with experimental data.
• Protein diffusivity follows a power law with protein length and is higher in pores with repulsive walls.
• The ratio of diffusivities in attractive versus repulsive pores shows maxima related to simultaneous wall interactions; diffusivity increases with temperature, exhibiting non-linear behavior near the folding temperature (Tf).

Conclusions:

• Protein transport in nanopores is significantly influenced by protein length, temperature, and wall interactions.
• A novel four-region 'phase diagram' is proposed to qualitatively describe the effects of pore size, temperature, and wall potentials on protein diffusivity.
• The findings provide valuable insights for designing nanoporous systems for controlled protein transport.