Computational Sensing and Discrimination of Two Sequence-Similar Peptide Hormone Miniproteins Utilizing Geometrically Varied Solid-State Nanopores

Abstract

1. Overview This dataset contains all configuration files, input structures, force field parameters, and trajectory outputs from all-atom molecular dynamics (MD) simulations and Adaptive Biasing Force (ABF) free energy calculations. The study investigates the single-molecule translocation dynamics and discrimination of two sequence-similar peptide hormones: Ex-4/pl14a (Exendin-4 analog, PDB ID: 2NAV, 30 residues, net charge: -1e) Thymosin-α1 (PDB ID: 2L9I, 28 residues, net charge: -4e) The peptides were modeled translocating through four geometrically distinct silicon nitride (Si3N4 solid-state nanopores (Circular, Rhombic, Square, and Triangular) with an identical cross-sectional area under an external electric field in 2 M KCl solution. 2. Archive Contents & File Hierarchy The dataset is organized into three primary zip archives: Archive 1: 1_2nav-nanopore_All-Atom_MD_namd.zip Contains all-atom MD simulation files for Ex-4/pl14a (PDB: 2NAV) under a 300 mV bias across 4 pore geometries and 4 initial translocation orientations: 1_namd_configuration_files/: NAMD configuration scripts for minimization, multi-stage equilibration (eq0.namd, eq1.namd, eq2.namd), and production runs (run0_pore-2nav_0.3v.namd through run3_...). 2_namd_input_files/: Organized by pore shape (01-pore-cir, 02-pore-rho, 03-pore-squ, 04-pore-tri) and orientation (01-orient1 to 04-orient4): Coordinate files (.pdb) and protein structure files (.psf). Harmonic restraint definition files for the Si3N4 membrane (siliconRest_1.0.pdb, siliconRest_2.0.pdb). Langevin temperature coupling definition files (*_all_langevin.pdb). 3_namd_output_files/: Stripped production trajectories (.dcd) and structure templates: No_water+SiN_*: 40 ns trajectories excluding water and pore atoms for peptide conformational analysis. No_water+ion_*: 40 ns trajectories including ions for calculating local ionic currents and free ion distributions. toppar/: Force field parameter and topology files (CHARMM36 protein, lipid, nucleic acid, CGenFF, TIP3P water/ions, and Resulting trajectories and free energy output files along the reaction coordinate (-25 Å ≤ z ≤ 25 Å). parameters: par_silicon_ions_NEW5.inp). Archive 2: 2_2l9i-nanopore_All-Atom_MD_namd.zip Contains all-atom MD simulation files for Thymosin-α1 (PDB: 2L9I) under identical conditions (300 mV, 2 M KCl, 4 geometries, 4 orientations): 1_namd_configuration_files/: Equilibration and production NAMD scripts. 2_namd_input_files/: Geometric configurations (01-pore-cir, 02-pore-rho, 03-pore-squ, 04-pore-tri) and orientation setups (01-orient1 to 04-orient4). 3_namd_output_files/: 40 ns stripped trajectory snapshots and .dcd files for analysis. toppar/: CHARMM36 and modified silicon nitride force field parameters. Archive 3: 3_ABF_simulation_namd.zip Contains free energy profile (Potential of Mean Force, PMF) calculations using the Adaptive Biasing Force (ABF) module implemented in NAMD: 001-2nav-nanopore/ (Ex-4/pl14a) & 002-2l9i-nanopore/ (Thymosin-α1): 1_namd_configuration_files/: Colvars collective variables configuration (abf.colvars), equilibration files, and ABF production scripts (e.g., run0_pore-2nav_0.45v.namd, run0_pore-2l9i_0.45v.namd). 2_namd_input_files/: Structural and constraint files for all 4 pore shapes oriented toward pore corners. 3_namd_output_files/: Resulting 10 ns trajectories along the reaction coordinate (-25 Å ≤ z ≤ 25 Å). toppar/: Corresponding force field libraries. 3. Simulation Parameters & Software Specifications MD Engine: NAMD3.0 (CUDA-accelerated) Colvars Module: Used for ABF free energy calculations along the translocation axis (z) Force Field: CHARMM36 all-atom additive force field (for peptides and ions); Customized parameters (par_silicon_ions_NEW5.inp) for Si3N4 membranes (Si: +0.76e, N: -0.57e). Water Model: Solvated with TIP3P water molecules; 2 M KCl neutral electrolyte. Thermostat/Barostat: Langevin dynamics (298 K) and Nosé-Hoover Langevin piston barostat (1 atm). Applied Transmembrane Voltage: 300 mV for standard translocation runs; 450 mV for ABF free energy profiling. 4. File Naming Conventions Pore Shapes: cir: Circular pore (d = 6.0 nm) rho: Rhombic pore (150°/30°) squ: Square pore (90°) tri: Triangular pore (60°) Orientations: orient1: 0° (aligned with pore axis) orient2: 45° clockwise tilt orient3: 90° clockwise tilt orient4: 135° clockwise tilt