Abstract
Single molecule protein sequencing would represent a disruptive burst in proteomic research with important biomedical impacts. Due to their success in DNA sequencing, nanopore based devices have been recently proposed as possible tools for the sequencing of peptide chains. One of the open questions in nanopore protein sequencing concerns the ability of such devices to provide different signals for all the 20 standard amino acids. Here, using equilibrium all-atom molecular dynamics simulations, we estimated the pore clogging in α-Hemolysin nanopore associated to 20 different homopeptides, one for each standard amino acid. Our results show that pore clogging is affected by amino acid volume, hydrophobicity and net charge. The equilibrium estimations are also supported by non-equilibrium runs for calculating the current blockades for selected homopeptides. Finally, we discuss the possibility to modify the α-Hemolysin nanopore, cutting a portion of the barrel region close to the trans side, to reduce spurious signals and, hence, to enhance the sensitivity of the nanopore.
Highlights
Nanopores have been demonstrated a great versatility in biosensing, as they can be employed to detect and analyze biological sample at single molecule level[1,2,3,4,5,6,7,8,9,10,11,12,13,14]
We studied the ionic current for four different homopeptide chains clogging the αHL nanopore via all-atom molecular dynamics simulations
The homopeptide is imported into the pore using steered molecular dynamics[39]
Summary
Significant differences among replicas of the same homopeptide are found for Ala, Gln, and Phe, while, Trp replicas do not show any significant variability, see Section S1 and Fig. S1b of Supporting Information This occurrence can be explained in term of the capability of smaller amino acids to explore a larger number of conformations inside the pore. On average, for a similar amino acid volume, the pore clogging is minimum for charged homopeptides and it progressively increases moving to hydrophilic and hydrophobic residues. The cited experimental results and our simulations suggest that biological pores can www.nature.com/scientificreports potentially been employed for protein sequencing several challenging issues, such as the translocation control, need to be solved[11]
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