Amyloid fibril structure modeling using protein threading and molecular dynamics simulations.

The elucidation of the structure of amyloid fibrils is an important step toward understanding the mechanism of amyloid formation and developing new reagents that could inhibit fibril formation. Here we describe an approach to modeling amyloid fibril structures using computational techniques, including protein threading and molecular dynamics simulations. Specifically, we introduce these methods using Abeta amyloid fibril modeling as an example. First, the amyloid protein sequence is threaded against a set of structural templates. Structural models are generated on the basis of threading alignments and are then subjected to molecular dynamic simulations to assess the stabilities of the model.