Simulation of solid-state and protein nanopores

The focus of this work is on characterization of the electric properties of aqueous ionic pores of nanoscale dimensions, or the nanopores. The nanopore types can be generally divided into three main categories: artificial solid-state devices, biologically occurring protein molecules forming nanopore structures, and hybrid structures.;Ionic conductance and other important electrostatic properties of solid-state silica nanopores are considered in this work. An analytical model is developed to calculate the surface charge density and the surface potential of a cylindrical nanopore. The obtained surface charge density is used as an input to a particle-based Brownian dynamics (BD) simulation software to characterize the ionic conduction process. The results are compared to a variety of published experimental data.;In order to characterize the protein nanopores, or the so called ion channels, on an atomic scale, several constrained dynamics algorithms are implemented within the existing BD framework. In particular, velocity-corrected SHAKE and LINCS algorithms are implemented to conserve the chemical bonds between atoms of the peptide chains throughout the simulation process. In addition, algorithms addressing the distribution of dielectric at the solid-liquid interface, as well as updating the ion's diffusion coefficient based on its position in the simulated system are developed and implemented to satisfy theoretical findings and results recently obtained with Molecular Dynamics (MD) simulations. The validity of the implemented algorithms is tested by simulating ionic transport through the well-studied OmpF ion channel and comparing the simulation results with experimental data.;The validated algorithms are subsequently applied to the simulation of a complex Shaker voltage-dependent potassium ion channel. The simulation results are compared to the published experimental, numerical, and theoretical findings. In particular, the implemented algorithms are applied to studying the ionic charge conduction through Shaker channel. The obtained currents in the tens of picoamperes corresponding to the transmembrane potential of 100mV are consistent with the published experimental findings. The potassium ion population profile inside the channel's selectivity filter is also considered in detail, and found to be in excellent agreement with the published results obtained with Molecular dynamics (MD) simulations of the KcsA protein with an identical selectivity filter. The beginning phase of the Shaker channel electromechanical deactivation is studied and found to strongly favor the paddle activation model suggested in the recent experimental works by MacKinnon et al.;Based on the obtained simulation results, the potential of the developed algorithms in detailed modeling of the transport processes in nanoscale pores is discussed. Also, a discussion on using BD simulation software to study electromechanical activation of voltage-dependent potassium ion channels is presented.