Figure 1.

The process of protein folding and aggregation. (A) Folding is presented based on the classical thermodynamic and kinetic principles. U, I, N*, N, TS refer to the unfolded state, partially-folded state, locally unfolded state, folded state and transient state, respectively. The conformational ensembles of U, I, N* are prone to aggregation; (B) Schematic representation of the protein aggregation process and the possible involved intermediates. This figure uses a monoclonal antibody as an example, but the general behaviors and principles are also applied to other proteins. The red arrows represent the non-native aggregation, while the dark blue arrows denote the native aggregation. The bidirectional arrows show the reversible steps, and the mono-directional arrows account for the irreversible process.