Translocation, Rejection and Trapping of Polyampholytes

Abstract

Polyampholytes (PA) are a special class of polymers comprising both positive and negative monomers along their sequence. Most proteins have positive and negative residues and are PAs. Proteins have a well-defined sequence while synthetic PAs have a random charge sequence. We investigated the translocation behavior of random polyampholyte chains through a pore under the action of an electric field by means of Monte Carlo simulations. The simulations incorporated a realistic translocation potential profile along an extended asymmetric pore and translocation was studied for both directions of engagement. The study was conducted from the perspective of statistics for disordered systems. The translocation behavior (translocation vs. rejection) was recorded for all 220 sequences comprised of N = 20 charged monomers. The results were compared with those for 107 random sequences of N = 40 to better demonstrate asymptotic laws. At early times, rejection was mainly controlled by the charge sequence of the head part, but late translocation/rejection was governed by the escape from a trapped state over an antagonistic barrier built up along the sequence. The probability distribution of translocation times from all successful attempts revealed a power-law tail. At finite times, there was a population of trapped sequences that relaxed very slowly (logarithmically) with time. If a subensemble of sequences with prescribed net charge was considered the power-law decay was steeper for a more favorable net charge. Our findings were rationalized by theoretical arguments developed for long chains. We also provided operational criteria for the translocation behavior of a sequence, explaining the selection by the translocation process. From the perspective of protein translocation, our findings can help rationalize the behavior of intrinsically disordered proteins (IDPs), which can be modeled as polyampholytes. Most IDP sequences have a strong net charge favoring translocation. Even for sequences with those large net charges, the translocation times remained very dispersed and the translocation was highly sequence-selective.

Translocation of Hydrophobic Polyelectrolytes under Electrical Field: Molecular Dynamics Study

“…In this work, we used simple periodic sequences in which extra barriers against translocation of antagonistic charges, as described previously for polyampholytes [15], were not present. Hydrophobicity has several effects.…”

“…In order to consider the channel properties, we modeled the translocation of the PEs through the α-hemolysin pore by applying a realistic force field extracted from the channel potential along the pore [14,15]. α-hemolysin is representative of the class of asymmetric pores and is widely used for the in vitro study of translocation.…”

“…The α-hemolysin channel has an electrostatic structure that influences the preferential translocation of negatively charged ions. In an early Monte Carlo simulation study [15], we incorporated realistic potential profiles of the α-hemolysin pore in a discrete manner to investigate the sequence dependence of the translocation of polyampholytes. In this study, we utilized the continuous force field of α-hemolysin to incorporate molecular dynamics simulations.…”

Polymer Dynamics: Bulk and Nanoconfined Polymers

“…Polyampholytes (PA) that have both positive and negative residues along the chain exhibit characteristic behaviors of translocation. Kim et al investigated the translocation process of random PA chains as a model for synthetic PAs under electric field via Monte Carlo simulations [ 7 ].…”