Enzyme inhibitory activity of marine alkaloid aaptamines for neurodegenerative diseases: An in silico study

The enzyme inhibitory activities of a dataset of 28 aaptamines are performed to identify potential multifunctional drugs for neurodegenerative diseases. First, the drug-like properties and pharmacokinetics (ADMET) study excluded 7 molecules, mostly for the non-permeability of the blood brain barrier. The binding activities of the remaining 21 candidates towards acetylcholinesterase (AChE), monoamine oxidase B (MAOB), and catechol-O-methyltransferase (COMT) enzymes are initially screened by molecular docking. The top binding complexes (A12@MAOB, A24@COMT, and A27@AChE) are simultaneously studied by molecular dynamics in water for 500 ns time-scale, and compared with the references such as safinamide (SAG), tolcapone (TOL) or donepezil (DON). The results show that two aaptamines A12 and A27 are well-positioned within the active pocket of the enzymes, exhibiting structural stability, with an RMSD of about 0.15-0.2 nm. MM-PBSA calculation indicates that the binding energy of the ligands to ..., , # Enzyme inhibitory activity of marine alkaloid aaptamines for neurodegenerative diseases: An in silico study

Dataset DOI: [10.5061/dryad.4f4qrfjqh](10.5061/dryad.4f4qrfjqh)

## Description of the data and file structure

The figures and tables presented here, along with the data presented in the main paper, provide comprehensive support for our research findings.

### List of Figures (supplementary files in Zenodo)

**Figure S1:** Optimized geometries, HOMO, LUMO, and ESP of the selected aaptamines A12, A24, and A27.

**Figure S2:** Time dependent RMSD (nm) of the complexes of SAG@MAOB, TOL@COMT, and DON@AChE in the time range 500 ns.

**Figure S3:** (Top) Gyration radius (nm) and (Bottom) Root-mean-square of fluctuation RMSF (nm) of the complexes A12@MAOB, A24@COMT, and A27@AChE in comparison with the corresponding references.

**Figure S4:** Total energy of A12@MAOB, A24@COMT, and their references, SAG@MAOB and TOL@COMT, in relationship with the number of H-bonds of the complexes.

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