Numerical simulation of conformational variability in biopolymer translocation throughwide nanopores

Maria Fyta,Simone Melchionna,Efthimios Kaxiras,Sauro Succi,Massimo Bernaschi

doi:10.1088/1742-5468/2009/06/p06009

Maria Fyta, Simone Melchionna + Show 3 more

Open Access

https://doi.org/10.1088/1742-5468/2009/06/p06009

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Abstract

Numerical results on the translocation of long biopolymers through mid-sized and widepores are presented. The simulations are based on a novel methodology which couplesmolecular motion to a mesoscopic fluid solvent. Thousands of events of long polymers (upto 8000 monomers) are monitored as they pass through nanopores. Comparison betweenthe different pore sizes shows that wide pores can host a larger number of multiplebiopolymer segments, as compared to smaller pores. The simulations provide clear evidenceof folding quantization in the translocation process as the biopolymers undertakemulti-folded configurations, characterized by a well-defined integer number of folds.Accordingly, the translocation time is no longer represented by a single-exponentpower-law dependence on the length, as is the case for single-file translocation throughnarrow pores. The folding quantization increases with the biopolymer length, whilethe rate of translocated beads at each time step is linearly correlated with thenumber of resident beads in the pore. Finally, analysis of the statistics over thetranslocation work unravels the importance of the hydrodynamic interactions in theprocess.

Highlights

Biological systems exhibit a complexity and diversity far richer than the simple solid or fluid systems traditionally studied in physics or chemistry
The translocation time is no longer represented by a single-exponent power law dependence on the length, as it is the case for single-file translocation through narrow pores
The folding quantization increases with the biopolymer length, while the rate of translocated beads at each time step is linearly correlated to the number of resident beads in the pore

Summary

Introduction

Biological systems exhibit a complexity and diversity far richer than the simple solid or fluid systems traditionally studied in physics or chemistry. The ultimate goal of these studies is to open a path for ultrafast DNA-sequencing by sensing the base-sensitive electronic signal as the biopolymer passes through a nanopore with attached electrodes The importance of this process has spawned a number of in vitro experiments, aimed at exploring the translocation process through micro-fabricated channels [4] under the effects of an external electric field, or through protein channels across cellular membranes [5, 6]. The translocation of biopolymers through (relatively) large pores was reported to exhibit the intriguing phenomenon of current-blockade quantization [1] This was interpreted as an indirect evidence that the polymer crosses the pore in the form of ”quantized” configurations, associated with integer values of the folding number, the number of strands simultaneously occupying the pore during the translocation. We elaborate more on this enriched dynamics and analyze in detail the phenomenon of folding quantization

Multiscale scheme

Configurational analysis

Quantization of the folding number

Forces influencing the translocation process

Findings

Summary