This site is also present, in variable conformations, in P. aeruginosa NAGK, but is missing from E. coli NAGK.
The N-terminal RAMP domain of SsoCas6 deviates from the standard motif in that the second RAMP helix (α2) that normally precedes β4 is missing and replaced by a loop with an extended conformation.
The fact that Thr671-Leu690 region known as Peptide A [ 15] is missing in fs-α1S suggests this 20-mer domain is not critical for the conformation change transmitted from the DHPR to the RyR1.
What is missing is their coherent application.
The necessary know-how is missing.
However, a systematic overview is missing.
We would like to stress here that, for standard VLS runs (where experimental information about possible binders and decoys are missing), the conformation selection is a major issue because it can greatly affect the VLS results, and also because it is very hard to establish "a priori" which conformer is able to provide the best results [33].
When molecular dynamics simulations of insufficient length are used to identify cryptic sites, allosteric sites, or pharmacologically relevant binding-pocket conformations for virtual-screening projects, the risk is that some suitable receptor conformations will be missed.
Additionally, reported crystal structures of MtIPMS exhibit different conformations for Q84 (including interactions with AcCoA, R80, R427, and E317) or are missing electron density for the side chain suggesting flexibility at this position.
The extent of the splicing is so extensive in AmNLG3e (9 of 11 β-strands of the central α-sheet are missing), that it is doubtful whether AmNLG3e, if folded, could assume an α/β hydrolase fold conformation.
