[Paper Review] Translocation Mobilities of Proteins in Nanopores: A Coarse-Grained Molecular Dynamics Study

Navaneeth Haridasan, Sridhar Kumar Kannam+2 more|arXiv (Cornell University)|Jan 26, 2018

Nanopore and Nanochannel Transport Studies3 citations

TL;DR

This study uses coarse-grained non-equilibrium molecular dynamics (NEMD) simulations to investigate streptavidin translocation through nanopores, revealing that translocation times increase by 3–4 orders of magnitude as nanopore radius approaches the protein's hydrodynamic radius. Results align well with the Einstein-Smoluchowski relation and a 1D biased diffusion model, offering predictive insights for protein sensing applications.

ABSTRACT

We investigate the translocation of a protein through model nanopores using coarse-grained (CG) non-equilibrium molecular dynamics (NEMD) simulations and compare the results with a continuum model. We considered the effects of nanopore confinement and external force on the translocation of streptavidin through nanopores of dimensions representative of experiments. As the nanopore radius approaches the protein hydrodynamic radius, the translocation times are observed to increase by 3 to 4 orders of magnitude. The mobilities are found to be in reasonable agreement with the prediction from Einstein-Smoluchowski relation where the diffusion coefficient was obtained from EMD simulations. The translocation times are found to be in good agreement with one-dimensional biased diffusion model. The results presented in this paper serve in rationalizing the experimental observations and provide strategic guidelines on choosing parametric conditions for applications such as protein sensors.

Motivation & Objective

• To understand the impact of nanopore confinement on protein translocation dynamics.
• To investigate how external forces influence translocation times of streptavidin through nanopores.
• To validate simulation results against continuum models such as the Einstein-Smoluchowski relation and 1D biased diffusion.
• To provide predictive guidelines for optimizing nanopore-based protein sensing systems.

Proposed method

• Employing coarse-grained (CG) non-equilibrium molecular dynamics (NEMD) simulations to model streptavidin translocation through synthetic nanopores.
• Using nanopore dimensions representative of experimental systems to ensure relevance to real-world applications.
• Comparing simulation outcomes with the Einstein-Smoluchowski relation by deriving the diffusion coefficient from equilibrium molecular dynamics (EMD) simulations.
• Applying a one-dimensional biased diffusion model to interpret and predict translocation times.
• Analyzing the effect of nanopore radius relative to the protein's hydrodynamic radius on translocation kinetics.

Experimental results

Research questions

• RQ1 How does nanopore confinement, particularly as the pore radius approaches the protein's hydrodynamic radius, affect translocation times?
• RQ2 To what extent do simulation results for protein mobilities agree with predictions from the Einstein-Smoluchowski relation?
• RQ3 How well does a one-dimensional biased diffusion model describe the observed translocation dynamics?
• RQ4 What are the implications of these findings for designing nanopore-based protein sensors?

Key findings

• Translocation times increase by 3 to 4 orders of magnitude as the nanopore radius approaches the hydrodynamic radius of streptavidin.
• Protein mobilities from simulations are in reasonable agreement with predictions from the Einstein-Smoluchowski relation when using diffusion coefficients from EMD simulations.
• Translocation times are well described by a one-dimensional biased diffusion model, supporting its use in modeling nanopore dynamics.
• The results rationalize experimental observations of prolonged translocation under steric confinement.
• The study provides actionable guidelines for selecting parametric conditions—such as pore size and applied force—for nanopore-based protein sensing applications.