Toward determining amyloid fibril structures using experimental constraints from Raman spectroscopy

Presenter's Name(s)

Maddie Harper

Conference Year

2024

Abstract

Amyloid fibrils are β-sheet rich protein aggregates that are implicated in diseases such as Alzheimer’s. Using Raman Spectroscopy, we demonstrated the distributions of peptide backbone amide C=O bond orientation and Ramachandran ψ dihedral angles can effectively guide molecular dynamics (MD) simulations to build structural models of amyloid fibrils. Our model systems, amylin20−29 and amyloid-β (Aβ)25−35, are oriented inextended β-sheet strands that are either parallel (amylin20−29 and Aβ25−35) or antiparallel (amylin20−29) β-sheet structures. Overall, our work lays the foundation for utilizing Raman spectroscopy as structural constraints in MD simulations to determine the three-dimensional molecular structural models of amyloid fibrils.

Primary Faculty Mentor Name

David Punihaole

Status

Graduate

Student College

College of Arts and Sciences

Program/Major

Chemistry

Primary Research Category

Physical Science

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Toward determining amyloid fibril structures using experimental constraints from Raman spectroscopy

Amyloid fibrils are β-sheet rich protein aggregates that are implicated in diseases such as Alzheimer’s. Using Raman Spectroscopy, we demonstrated the distributions of peptide backbone amide C=O bond orientation and Ramachandran ψ dihedral angles can effectively guide molecular dynamics (MD) simulations to build structural models of amyloid fibrils. Our model systems, amylin20−29 and amyloid-β (Aβ)25−35, are oriented inextended β-sheet strands that are either parallel (amylin20−29 and Aβ25−35) or antiparallel (amylin20−29) β-sheet structures. Overall, our work lays the foundation for utilizing Raman spectroscopy as structural constraints in MD simulations to determine the three-dimensional molecular structural models of amyloid fibrils.