Biology subjects

Sur, P.

Publications and source records attributed to Sur, P..

4 recordsLinked to original sources

bioRxiv2026

Breaking Pore Symmetry to Prolong DNA Residence in Solid-State Nanopores

Rapid DNA transport limits the temporal resolution of solid-state nanopore sensing. Here we show that breaking pore symmetry through geometric inclination produces exceptionally prolonged DNA residence without surface functionalization or external trapping. For 500-base-pair double-stranded (ds) DNA ,13 nm diameter SiNx pores in tilted membranes exhibit a distinct long-lived population with a mean dwell time of 11.1 seconds at 600 mV bias, exceeding previously reported dsDNA dwell times by at-least 4 orders of magnitude. Controlled pore tilting reproduces the population of prolonged events, whose prevalence and duration depend on ionic strength. TEM-EELS based thickness measurements exclude substantial membrane-thickness differences, while continuum and atomistic simulations support a mechanism coupling electric-field redistribution to off-axis DNA motion, increased pore-wall contact and suppressed axial mobility. These findings establish geometric inclination as a passive design variable for engineering molecular residence in solid-state nanopores and provide a route towards longer observation windows for single-molecule sensing.

bioengineering↗

bioRxiv2026

Nanopore Electrometry Resolves Peptide Charge Patterns beyond Ionic-Current Blockade

Localized measurements of electric fields offer a promising route to expand the information content of nanopore-based single-molecule sensing beyond conventional ionic-current blockade. Here, using all-atom molecular dynamics simulations with virtual electric-field probes placed around a graphene nanopore, we show that the local electric-field captures the presence, and distribution of charged amino acids as the peptides translocate through the pore. These field signatures create reproducible peptide-specific fingerprints across independent translocation events and enable substantially improved discrimination between peptides compared with ionic-current traces obtained under the same simulation conditions. Our results suggest that localized nanopore electrometry can provide a complementary, information-rich readout of peptide charge order that is largely inaccessible to conventional current blockade-based measurement. This study establishes a simulation-guided framework for integrating nanoscale electrometry with nanopore platforms for future peptide and protein analysis.

biophysics↗

bioRxiv2026

PTM-Driven Reshaping of the Peptide Translocation Landscape in Bilayer Graphene Nanopores

Post-translational modifications (PTMs) underpin much of protein regulation, yet their single-molecule readout remains a challenge in nanopore proteomics. While biological nanopores have shown exquisite PTM sensitivity, the microscopic mechanisms by which PTMs perturb signals in solid-state nanopores are largely unexplored. Here, we use all-atom molecular dynamics to investigate how three common PTMs, acetylation, phosphorylation, and methylation, modulate the translocation of a cancer-relevant p53 peptide fragment through a bilayer graphene nanopore. We find that PTMs remodel the translocation landscape far more strongly at the level of dwell-time statistics than at the level of mean current blockade. Acetylation enhances peptide-graphene adhesion and substantially slows transport, with adjacent acetylations producing the longest residence times due to cooperative interfacial interactions, while remotely spaced acetylations yield broader, heterogeneous dynamics. Phosphorylation introduces a negative charge that increases dwell time through an electrostatic tug-of-war, while also generating the largest current blockade among the PTMs studied. In contrast, methylation minimally perturbs translocation due to weak pore interactions and preserved charge. Combining dwell time with relative blockade features enables a simple linear SVM classifier to reliably distinguish unmodified, acetylated, and phosphorylated states. These results establish mechanistic design principles for PTM detection using solid-state nanopores and delineate which classes of PTMs are the most amenable to single-molecule detection with these devices.

biophysics↗

bioRxiv2025

Orientation Dependence of Current Blockade in Single Amino Acid Translocation through a Graphene Nanopore

After successful commercialization of DNA sequencing with biological nanopores, the next frontier of the nanopore technology is protein sequencing which is far more daunting a task. Molecules passing through solid-state nanopores produce current blockades that correlate with their volume linearly in the simplest conceivable model. As thinner membranes provide better volume sensitivity, 2D materials such as Graphene, MoS2 membranes have been explored. Molecular dynamics studies, mostly of homogeneous polypeptide chains translocating through 2D membranes, have been reported. In this paper, we study the translocation of all the twenty single amino acids through monolayer and bilayer graphene nanopores using all-atom molecular dynamics. These studies were motivated by the fact that single amino-acids being the building blocks of peptide chains, can help us understand pore-molecule interactions during translocations at a more basic level, for instance, avoiding neighbor effects present in a chain. We show here that the correlation between the ionic current blockade and the volume of single amino acids is strongly affected by their orientation at the pore, especially when the molecule is static at pore. We explain this phenomenon by the fact that with increasing vdW volume, the amino acid in a particular orientation, has longer projection along the perpendicular direction of the pore plane. We demonstrate distinctive current and force signals for different amino-acid translocation. We observe that some of the smaller amino acids with low molecular volume produce disproportionately high current blockades in a particular orientation due to their low structural fluctuations during translocation. We investigate how dipole-moment (of the translocating amino-acids) and its alignment with electric field in the pore can be linked with our observations.

biophysics↗