Computational protocol: A Porphodimethene Chemical Inhibitor of Uroporphyrinogen Decarboxylase

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Protocol publication

[…] Various potential target compounds were drawn using ChemDraw (Perkin Elmer, Waltham, Massachusetts) based on their similarity to coproporphyrinogen, uroporphyrinogen, and a previously suggested endogenous inhibitor (, ) . PI-16, the only chemically stable target compound within the set of proposed inhibitors, was docked to wildtype human UROD crystal structures (PDB codes 1R3Q and 1R3Y, ) using Schrödinger Suite and Glide software (Schrödinger, Munich, Germany) –. The multistep Schrödinger protein preparation wizard tool (PPrep) was used. Protein minimization used the OPLS-2005 force field with the Polak-Ribiere Conjugate Gradient (PRCG) algorithm. The LigPrep module was used for ligand preparation. All ligands were minimized using the OPLS-2005 force fields with the appropriate default settings. At least 10 docking poses and the corresponding scores were evaluated in both the standard precision and extra precision mode (Glide XP) for each potential target. Coproporphyrin (the oxidized product of normal UROD catalysis) was used as a control because it is the only known ligand that has been co-crystallized with UROD. […]

Pipeline specifications

Software tools ChemDraw, Glide, LigPrep
Applications Drug design, Protein interaction analysis
Organisms Homo sapiens
Diseases Neoplasms
Chemicals Cisplatin, Heme, Oxygen, Porphobilinogen