Computational modeling of peptide-mediated charge transport and membrane-associated phenomena
type: CreativeWork
description: Proteins and membranes play a crucial role in fueling cellular activity and maintaining cellular homeostasis. Proteins act as energy conduits within cells by shuttling electrons through a series of reactions to fuel the synthesis of adenosine triphosphate (ATP). In mitochondria, membranes provide an ideal structural framework to efficiently carry out the electron transport that forms the basis of biological energy production processes. By relying on the principle of compartmentalization, chemical redox processes within the cell can reliably proceed forward and avoid back reactions. Disturbances to both membrane and protein structure are therefore crucially linked to disease, and as the role of membrane and protein biology is uncovered, the need to understand the molecular and atomic bases of protein-, peptide-, and membrane-mediated charge transport remains a paramount challenge. Despite recent progress, theoretical and computational modeling of the complex interplay between chemical composition, structure, and function of these biomolecules remains challenging. To address these challenges, I have pursued the characterization of peptide-mediated charge transport and membrane-associate phenomena, particularly through the use of molecular dynamics (MD) simulations. MD simulations set a standard for revealing the underlying molecular mechanisms of biophysical and biochemical experiments. It is a particularly effective technique for uncovering atomic-level interactions that contribute to experimental observables. First, I explore the structure-activity relationships governing transmembrane ion conductance mediated by Aβ(1-42) peptides. Enabled by precise NMR structures of putative neurodegenerative structures of Aβ(1-42) oligomers, our simulations revealed a mechanism of membrane disruption in which permeation occurred through lipid-stabilized pores mediated by hydrophilic residues located on the core β-sheet edges of the Aβ(1-42) oligomers. Such behavior resembles the …
abstract: Proteins and membranes play a crucial role in fueling cellular activity and maintaining cellular homeostasis. Proteins act as energy conduits within cells by shuttling electrons through a series of reactions to fuel the synthesis of adenosine triphosphate (ATP). In mitochondria, membranes provide an ideal structural framework to efficiently carry out the electron transport that forms the basis of biological energy production processes. By relying on the principle of compartmentalization, chemical redox processes within the cell can reliably proceed forward and avoid back reactions. Disturbances to both membrane and protein structure are therefore crucially linked to disease, and as the role of membrane and protein biology is uncovered, the need to understand the molecular and atomic bases of protein-, peptide-, and membrane-mediated charge transport remains a paramount challenge. Despite recent progress, theoretical and computational modeling of the complex interplay between chemical composition, structure, and function of these biomolecules remains challenging. To address these challenges, I have pursued the characterization of peptide-mediated charge transport and membrane-associate phenomena, particularly through the use of molecular dynamics (MD) simulations. MD simulations set a standard for revealing the underlying molecular mechanisms of biophysical and biochemical experiments. It is a particularly effective technique for uncovering atomic-level interactions that contribute to experimental observables. First, I explore the structure-activity relationships governing transmembrane ion conductance mediated by Aβ(1-42) peptides. Enabled by precise NMR structures of putative neurodegenerative structures of Aβ(1-42) oligomers, our simulations revealed a mechanism of membrane disruption in which permeation occurred through lipid-stabilized pores mediated by hydrophilic residues located on the core β-sheet edges of the Aβ(1-42) oligomers. Such behavior resembles the …
author: Meigooni, Moeen Shamseddin
language: eng
language: en
keywords: Electron Transport, Molecular Dynamics, Membrane Curvature, Peptide Conductance
date published: 2024-12
date modified: 2026-07-22T22:25:03Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: https://hdl.handle.net/2142/127339