Computational analysis of complex systems: alpha-3-beta-2 nicotinic acetylcholine receptor and type I and II silicon clathrates

Abstract

Computational simulations allow for the detailed study of complex systems and allow the opportunity to provide insight and understanding on the molecular level. The motivation of this thesis is to probe a higher level understanding of realistic problems through the use of advanced biasing techniques. The thesis is split into two distinct projects. Part I is the analysis of a nicotinic acetylcholine receptor (nAChR), involving the initial actions of the gating mechanism and the computational hurdles required to create a realistic simulation environment. Ligand binding affinity and biased molecular dynamics results indicate that productive gating of an [alpha-3-beta-2] nAChR may be driven by the structural properties of the C-loop. Part II examines the thermodynamic and kinetic driving forces and their effects on sodium diffusion in type I and type II Si-clathrates. Sodium concentration was found to have a significant effect on the transition barrier heights between cages and shifted the thermodynamics in favor of a sodium deficient environment. In addition, structural differences between type I and type II clathrates play a central role in the ability to remove sodium from the clathrate, and the pathway hypothesis suggested in this thesis may provide insight to possible guest removal from other clathrate systems.