Atomic-Scale Simulations of Amyloid Beta Fibrils with Dismantling Polymer-Peptide Conjugates

Jeffery S. Moore, University of Illinois at Urbana-Champaign

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Jeffery S. Moore, Jeff Moore, Rezvan Shahoei, Joao Ribeiro, Moeen Meigooni, Andres Arango, Archit Vasan, Nandan Haloi, Sepehr Dehghanighahnaviyeh, Jimmy Do, Giuseppe Leonardo Licari, Soumyo Sen, Mariano Spivak, Zhaleh Ghaemi

Aggregation of amyloid beta (Aβ) proteins is believed to play a fundamental role in Alzheimer's disease. The aim of this proposal is to reach a better understanding of the mechanism by which novel multivalent polymer-peptide conjugates (mPPCs) might disaggregate or inhibit the Aβ fibril formation. The existence of suitable structural data for the Aβ protein made possible the building of an all-atom model of the fibril, which will be employed for molecular dynamics simulations. This proposal focuses on the structural and mechanical properties of the fibril from a molecular point of view. Additionally, the proposal explores systems containing both the fibril and mPPC platforms. The molecular interactions revealed by these simulations can be used in the design of more efficient dismantling agents. The completion of this proposal requires massive computing resources. Therefore, this project is only feasible on supercomputers such as Blue Waters. The size of the system, ~2 million atoms, and the involved time scales, in the order of hundreds of nanoseconds, are certainly prohibitive for small computer clusters.