Figure 2: The distribution of flap domain to active site distances from MD simulations highlights that the flap is a highly flexible domain that can adopt more open conformations than seen in the AlphaFold-predicted structure.

A) The MSM-weighted distribution of average distances between the flap domain (defined as residue 219–295) and the active site (residues 105, 192, 314, and 366) backbones shows two peaks as well as long tails that highlight low probability highly closed and highly open conformations. The dashed red line indicates the same distance measured for the AlphaFold-predicted structure. B) These structures depict a highly closed, an intermediate, and a highly open MSM cluster center. The flap domain is colored in cyan. Circles with Roman numerals indicate where these structures fall in the distribution.