Long time dynamic simulations: exploring the folding pathways of an Alzheimer's amyloid Abeta-peptide.
We describe the MaxFlux algorithm for the computation of likely pathways for global macromolecular conformational transitions. The algorithm assumes an overdamped diffusive dynamics for the biomolecule, appropriate to large scale conformational changes. As an application of the MaxFlux method, we explore conformational transitions between alpha-helical, collapsed coil, and beta-sheet conformations of an amyloid Abeta-peptide. The resulting transition pathways are analyzed in terms of the mechanism of conformational transition and the progression of the peptide energetics in both an aqueous and a membrane-mimicking nonpolar solvent.
Straub
John E
JE
Department of Chemistry, Boston University, Boston, Massachusetts 02215, USA.
Guevara
Javier
J
Huo
Shuanghong
S
Lee
Jonathan P
JP
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D003198:Computer Simulation; D006801:Humans; D007700:Kinetics; D017510:Protein Folding; D017433:Protein Structure, Secondary / Q000187:drug effects; D012997:Solvents / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D012997:Solvents