Dataset Information

The Manipulation of the Internal Hydrophobicity of FraC Nanopores Augments Peptide Capture and Recognition.

ABSTRACT: The detection of analytes and the sequencing of DNA using biological nanopores have seen major advances over recent years. The analysis of proteins and peptides with nanopores, however, is complicated by the complex physicochemical structure of polypeptides and the lack of understanding of the mechanism of capture and recognition of polypeptides by nanopores. In this work, we show that introducing aromatic amino acids at precise positions within the lumen of α-helical fragaceatoxin C (FraC) nanopores increased the capture frequency of peptides and largely improved the discrimination among peptides of similar size. Molecular dynamics simulations determined the sensing region of the nanopore, elucidated the microscopic mechanism enabling accurate characterization of the peptides via ionic current blockades in FraC, and characterized the effect of the pore modification on peptide discrimination. This work provides insights to improve the recognition and to augment the capture of peptides by nanopores, which is important for developing a real-time and single-molecule size analyzer for peptide recognition and identification.

SUBMITTER: Lucas FLR

PROVIDER: S-EPMC8223486 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Manipulation of the Internal Hydrophobicity of FraC Nanopores Augments Peptide Capture and Recognition.

Lucas Florian Leonardus Rudolfus FLR Sarthak Kumar K Lenting Erica Mariska EM Coltan David D van der Heide Nieck Jordy NJ Versloot Roderick Corstiaan Abraham RCA Aksimentiev Aleksei A Maglia Giovanni G

ACS nano 20210601 6

The detection of analytes and the sequencing of DNA using biological nanopores have seen major advances over recent years. The analysis of proteins and peptides with nanopores, however, is complicated by the complex physicochemical structure of polypeptides and the lack of understanding of the mechanism of capture and recognition of polypeptides by nanopores. In this work, we show that introducing aromatic amino acids at precise positions within the lumen of α-helical fragaceatoxin C (FraC) nano ...[more]

PMID: 34060809

Similar Datasets

Project description:The integration of local heat sources with solid-state nanopores offers new means for controlling the transmembrane transport of charged biomacromolecules. In the case of electrophoretic transport of DNA, recent experimental studies revealed unexpected temperature dependences of the DNA capture rate, the DNA translocation velocity, and the ionic current blockades produced by the presence of DNA in the nanopore. Here, we report the results of all-atom molecular dynamics simulations that elucidated the effect of temperature on the key microscopic processes governing electric field-driven transport of DNA through nanopores. Mimicking the experimental setup, we simulated the capture and subsequent translocation of short DNA duplexes through a locally heated nanopore at several temperatures and electrolyte conditions. The temperature dependence of ion mobility at the DNA surface was found to cause the dependence of the relative conductance blockades on temperature. To the first order, the effective force on DNA in the nanopore was found to be independent of temperature, despite a considerable reduction of solution viscosity. The temperature dependence of the solution viscosity was found to make DNA translocations faster for a uniformly heated system but not in the case of local heating that does not affect viscosity of solution surrounding the untranslocated part of the molecule. Increasing solution temperature was also found to reduce the lifetime of bonds formed between cations and DNA. Using a flow suppression algorithm, we were able to separate the effects of electro-osmotic flow and direct ion binding, finding the reduced durations of DNA-ion bonds to increase, albeit weakly, the effective force experienced by DNA in an electric field. Unexpectedly, our simulations revealed a considerable temperature dependence of solvent velocity at the DNA surface-slip velocity, an effect that can alter hydrodynamic coupling between the motion of DNA and the surrounding fluid.

Dataset Information

The Manipulation of the Internal Hydrophobicity of FraC Nanopores Augments Peptide Capture and Recognition.

Publications

The Manipulation of the Internal Hydrophobicity of FraC Nanopores Augments Peptide Capture and Recognition.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets