(577c) Atomistic Simulation of Polyglutamine in Solution | AIChE

(577c) Atomistic Simulation of Polyglutamine in Solution

Authors 

Fluitt, A. M. - Presenter, University of Nebraska-Lincoln
de Pablo, J. J., University of Chicago



Peptides containing a long repeat of glutamine residues, called polyglutamine or polyQ, are widely studied, both as a useful model system for protein misfolding and aggregation and in relation to their own role in the molecular-level pathogenesis of neurodegenerative disease. The early-stage aggregates, or oligomers, of polyQ-containing peptides are believed to be especially cytotoxic, but their characterization is frustrated by their small size and transient nature. A combination of atomistic molecular dynamics simulations and nonlinear spectroscopies possesses the structural and temporal resolution necessary for characterizing polyQ oligomers. The reliability of simulation results depends in part on the accuracy of the potential energy functions which describe intermolecular interactions. In this work, we systematically analyze the performance of several atomistic models of biomolecules, or “force fields,” in reproducing two essential properties of simple polyQ peptides in dilute aqueous solution: its lack of regular secondary structure and its poor solvation by water that drives collapse. We observe substantial differences in the predicted properties depending on the force field used. We identify the force fields that achieve good qualitative and quantitative agreement with available experimental data, and we discuss the implications of our results as they relate to the study of polyQ and intrinsically disordered peptides.