Computational tools are increasingly being applied to solve the protein aggregation problem, providing insight into amyloid structures and aggregation mechanisms. The paradigm of Aβ amyloid structure elucidation provides an example of an innovative experimental design and endeavor, echoing the computational testing of possible molecular associations, all reflected in the current Ma-Nussinov-Tycko model of the Aβ amyloid. Simulations have shown that dimer formation can lock some misfolded conformations, and catalyze the shift of the equilibrium away from the native state. In most cases, a stable amyloid seed requires at least two-layered β-sheets with properly registered side-chains. Under kinetic control, the final protein aggregations are the outcome of maximizing the van der Waals interactions between side chains and backbone hydrogen bonds.