Table 3 Docking energy scores (S) and hot spots involved in binding for APPA (the co-crystalized compound), amiodaron (the drug candidate), and the reported compounds in the acid sphingomyelinase active site
Compound | Docking score (S) (kcal/mol) | Hot spots involved in binding |
|---|---|---|
APPA (Co-crystalized ligand) | − 28.75 | Asn316, His280, and Zn(II) ions |
Amiodarone (Drug candidate) | − 10.43 | Tyr572 |
Alverine | − 8.22 | Ile 487 |
Astemizole | − 10.81 | Asn488 and His457 |
Aprindine | − 8.41 | Asn488 and Thr456 |
Amlodipine | − 9.14 | Zn(II) ions |
Ambroxol | − 8.54 | His455, His457, Glu386, and Zn(II) ions |
Amitriptyline | − 7.94 | Ile 487 |
Benztropine | − 8.18 | ––––- |
Bepridil | − 10.47 | Asn488 |
Biperidene | − 7.96 | Thr456 |
Camylofine | − 8.55 | His280 and His455 |
Carvedilol | − 11.28 | ––––- |
Cepharanthine | − 11.06 | Asn316, His280, Ile487, and His457 |
Clofazimine | − 10.37 | Ile 487 |
Clemastine | − 8.40 | ––––- |
Cloperastine | − 8.04 | ––––- |
Chlorprothixene | − 7.86 | Asn323, His280, and Phe486 |
Chlorpromazine | − 8.29 | Ile 487 |
Clomiphene | − 8.95 | ––––- |
Clomipramine | − 8.31 | His280 |
Conessine | − 8.33 | ––––- |
Cyclobenzaprine | − 8.03 | Asn488 and His457 |
Cyproheptadine | − 8.45 | ––––- |
Desipramine | − 8.38 | Asn316 and Glu386 |
Desloratadine | − 8.77 | Asn323 and His280 |
Dicycloverine | − 7.53 | His280 and His457 |
Dilazep | − 12.58 | His457 |
Dimebon | − 9.41 | Asn488 |
Doxepine | − 8.36 | Asn488 |
Drofenine | − 8.08 | Asn316 and His317 |
Emetine | − 11.65 | ––––- |
Fendeline | − 9.06 | Ile487 |
Flupenthixol | − 10.39 | His455, His280, His457, Ile487, and Zn(II) ions |
Fluoxetine | − 10.09 | His457, Ile487, and Lys103 |
Fluvoxamine | − 9.37 | His455, Ile487, and Zn(II) ion |
Fluphenazine | − 9.59 | His455, His317, and Glu386 |
Flunarizine | − 9.20 | His317 |
Hydroxyzine | − 10.96 | His455, Ile487, and Zn(II) ions |
Imipramine | − 7.76 | Asn488 |
Loperamide | − 10.13 | Asn316, His280, and Lys103 |
Loratadine | − 8.47 | ––––- |
Maproteline | − 7.96 | His280, Thr456, and His457 |
Melatonine | − 9.23 | His280 |
Mebhydroline | − 8.02 | Asn488 |
Mebeverine | − 11.14 | His457 |
Mibefradil | − 10.09 | Asn488 and Glu386 |
Norfluoxetine | − 10.34 | His280 and Zn(II) ions |
Nortriptyline | − 7.49 | His457 |
Paroxetine | − 10.23 | Asn488 |
Perphenazine | − 9.78 | His455, His317, and Zn(II) ions |
Pimozide | − 11.29 | His280, His317, and Asn488 |
Profenamine | − 7.72 | His317 |
Promethazine | − 7.62 | Ile487 |
Promazine | − 8.09 | Ile487 |
Protriptyline | − 8.48 | Ile487 |
Quinacrine | − 10.19 | His280 |
Sertindole | − 10.55 | His457 |
Solasodine | − 8.64 | His317 |
Sertraline | − 7.77 | His317 |
Suloctidil | − 8.64 | His455 |
Tamoxifene | − 8.56 | Phe486 |
Thioridazine | − 8.00 | His317 |
Tomatidine | − 8.85 | His280 |
Terfenadine | − 10.39 | His455 and His457 |
Trifluoperazine | − 10.22 | Ile487 |
Triflupromazine | − 8.72 | Asn488 |
Trimipramine | − 7.79 | His280, Asn323, and Phe486 |
Zolantidine | − 9.13 | His457 and Ile487 |