Introduction: Solid-state nanopores have emerged as a powerful platform for DNA sequencing and biomolecular analysis, offering precise control over pore geometry and material properties. Recent advances in nanofabrication enable the creation of nanopores with nanoscale precision in both size and shape. These structural parameters significantly influence the ionic transport characteristics and translocation behavior of DNA and other biomolecules. To better understand these effects and optimize nanopore design, we propose using molecular dynamics (MD) simulations to study the ionic and molecular transport phenomena associated with various nanopore geometries. Objectives: 1. Investigate how different nanopore shapes (cylindrical, conical, hourglass, elliptical, etc.) affect ionic current and DNA translocation dynamics. 2. Correlate experimental ionic current measurements with MD-simulated transport behaviors. 3. Develop a theoretical framework to explain observed experimental trends and guide future nanopore fabrication. Methodology: • Nanopore Design & Fabrication: We have established methods to fabricate solid-state nanopores with sub-nanometer precision, allowing for systematic variation in shape and size. • Experimental Data Collection: We conduct DNA translocation experiments, measuring ionic currents to detect changes due to nanopore shape variations. • Molecular Dynamics Simulations: Using MD simulations, we model DNA and biomolecule transport through differently shaped nanopores, analyzing key parameters such as: o Ionic current fluctuations o Molecular conformations and interactions within the pore o Electro-osmotic flow and hydrodynamic effects • Validation & Prediction: By comparing simulated results with experimental data, we refine our understanding of the physical mechanisms governing translocation. This approach will enable the prediction of optimal nanopore designs for improved sequencing accuracy and sensitivity. Expected Outcomes: This study will establish a direct link between nanopore geometry and ionic transport characteristics, providing mechanistic insights into DNA sequencing performance. The results will serve as a guide for experimentalists, helping refine nanopore designs to enhance sequencing precision and efficiency.