Origins of barriers and barrierless folding in BBL

In contrast to classical chemical phenomenology, theory suggests that proteins may undergo downhill folding without an activation barrier under certain thermodynamic conditions. Recently, the BBL protein was proposed to fold by such a downhill scenario, but discrepancies between experimental results found in different groups argue against this. After briefly reviewing the major experimental studies of the BBL folding mechanism, we show that simulations of both coarse-grained and atomistic models can reconcile the seemingly conflicting observations.