A Statistical Model for Translocation of Structured Polypeptide Chains through Nanopores

被引：40

作者：

Ammenti, Alessandro ^{[2
]}

Cecconi, Fabio ^{[1
]}

Marconi, Umberto Marini Bettolo ^{[3
]}

Vulpiani, Angelo ^{[4
]}

机构：

[1] Ctr Stat Mech & Complex, Ist Sistemi Complessi, CNR, INFM, I-00185 Rome, Italy

[2] Univ Perugia, Dipartimento Fis, I-06123 Perugia, Italy

[3] Univ Camerino, Dipartimento Fis, I-68032 Camerino, MC, Italy

[4] Univ Roma La Sapienza, Dipartimento Fis, Ist Nazl Fis Nucl, I-00185 Rome, Italy

来源：

JOURNAL OF PHYSICAL CHEMISTRY B | 2009年 / 113卷 / 30期

关键词：

MOLECULAR-DYNAMICS SIMULATIONS; HISTOGRAM ANALYSIS METHOD; FREE-ENERGY CALCULATIONS; PROTEIN TRANSLOCATION; POLYNUCLEOTIDE MOLECULES; POLYMER TRANSLOCATION; MEMBRANE; TRANSPORT; UBIQUITIN; PORE;

D O I：

10.1021/jp900947f

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

The translocation process of a globular protein (ubiquitin) across a cylindrical nanopore is studied via molecular dynamics simulations. The ubiquitin is described by a native-centric model on a C-a carbon backbone to investigate the influence of protein-like structural properties on the translocation mechanism. A thermodynamical and kinetic characterization of the process is obtained by studying the statistics of blockage times, the mobility, and the translocation probability as a function of the pulling force F acting in the pore. The transport dynamics Occurs when the force exceeds a threshold F-c depending on a free-energy barrier that ubiquitin has to overcome in order to slide along the channel. Such a barrier results from competition of the unfolding energy and the entropy associated with the confinement effects of the pore. We implement appropriate umbrella sampling simulations to compute the free-energy profile as a function of the position of the ubiquitin center of mass inside of the channel (reaction coordinate). This free energy is then used to construct a phenomenological drift-diffusion model in the reaction coordinate which explains and reproduces the behavior of the observables during the translocation.

引用

页码：10348 / 10356

页数：9

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