イン・シリコ解析によるタンパク質L-イソアスパルチル（D-アスパルチル）O-メチルトランスフェラーゼとアスパラギン酸異性体含有ペプチド基質との結合様式予測
Aspartic acid (Asp) residues in human proteins undergo isomerization, yielding L-α-Asp, L-β-Asp, D-α-Asp, and D-β-Asp forms, with D-β-Asp being the most abundant. Protein L-isoaspartyl (D-aspartyl) O-methyltransferase (PIMT) is a candidate repair enzyme that recognizes L-β-Asp and D-α-Asp and catalyzes side-chain methylation. Computational docking and molecular dynamics simulations were applied to characterize PIMT–peptide interactions for all four isomers. For substrate peptides (L-β-Asp and D-α-Asp), carboxyl groups were recognized in comparable orientations and C-terminal regions occupied similar positions on PIMT. Non-substrate peptides (L-α-Asp and D-β-Asp) showed markedly different binding geometries, characterized by intramolecular rather than intermolecular hydrogen bonds and more rigid peptide conformations. These findings demonstrate that in silico methods can reliably discriminate substrates from non-substrates, offering a computational complement to experimental screening approaches.
PIMT recognizes the carboxyl groups of L-β-Asp and D-α-Asp in similar orientations to catalyze side-chain methylation; non-substrate isomers form intramolecular hydrogen bonds that rigidify peptide conformation and prevent productive binding.
This is basic research at the cellular or molecular level. For human application, inhalation is the most promising delivery route, but inhalation carries explosion risk and concentration matters (empirical LFL of 10%; high-concentration devices are not recommended).
See also:
https://h2-papers.org/en/papers/25758062