Thesis Title

Modeling and Computer Simulation of Polypeptide Aggregation Using an Intermediate Resolution Protein Model (PRIME)

Systems of Interest

  • Polyalanine
  • Lung Surfactant Protein C

Methods and Software

  • Discontinuous Molecular Dynamics (DMD) Simulations
  • Fortan 90
  • Rasmol molecular visualization program


Protein aggregation is associated with several neurodegenerative diseases, such as Alzheimer's, Parkinson's, Huntington's, and prion diseases such as Mad Cow or Creutzfeld Jakob. These aggregates form ordered structures known as amyloid fibrils, which are toxic to surrounding tissues. Experimental studies have shown under which conditions fibrils form, but give no details about how or why they form. Studying the aggregation mechanism using PRIME, an intermediate resolution protein model developed in our group allows us to simulate peptide fibril formation beginning from a random coil configuration. This is not possible using all-atom simulation techniques. PRIME captures the essential features of protein interactions and geometry, while simplifying the protein representation, producing simulated results in a reasonable time frame. An understanding of the aggregation mechanism will allow for progress in treating or curing the aforementioned neurodegenerative diseases.

Polyalanine aggregation

Computer simulation of protein aggregation using Discontinuous Molecular Dynamics (DMD) will allow us to study the molecular level behavior of the different reactions between peptides, which is impossible in laboratory experiments. After expanding the PRIME model to include all twenty amino acid residues found in proteins, specific protein sequences known to form fibrils in biological systems, such as that of lung surfactant protein C, can be simulated in order to determine the basic mechanism underlying the kinetics of fibril formation.