Table 1. All Residues in the Set X (i.e., solvent-accessible in the intermediates but inaccessible in the simulated crystal conformations, see text) That Belong to the TTDI^a.

	“int.-solv.-acc.”	max SASArel (OfCC,IfCC) [%]
successful SCAM predictions	I61, I213, M395?	3.5, 2.3, 13.1
unsuccessful SCAM predictions	V209?	4.8
new SCAM predictions	L54, V62, L66?, V198, A205	2.1, 0.0, 3.7, 2.7, 0.8

^aSolvent-accessible residues predicted from the simulations are listed as “successful SCAM prediction” if the position is known (e.g., from published SCAMs^5,54,55) to be solvent accessible in GltPh or its corresponding site of an EAAT homologue; it is identified as “unsuccessful SCAM prediction” if this position has been tested, e.g., with SCAM but not found to be solvent accessible so far;⁵⁴ it is listed in “new SCAM predictions” if to date, to the best of our knowledge, no solvent-accessibility measurements have been performed on this residue in GltPh or its EAAT counterpart. Residues marked as ^? also showed some solvent accessibilty in the end conformations, measuring one or more average water molecules within 3 Å of the residue’s side chain (see Figure SI7, Supporting Information). In the “max SASA_rel” column, for each residue in the set X we list the maximum SASA_rel values observed in the OfCC and IfCC.