Computational protocol: Computer-aided design of temozolomide derivatives based on alkylglycerone phosphate synthase structure with isothiocyanate and their pharmacokinetic/toxicity prediction and anti-tumor activity in vitro

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Protocol publication

[…] Protein structure processing was completed with the QikProp module of Schrodinger Suite 2009 software (Schrodinger, LLC, Cambridge, MA, USA). The downloaded AGPS target crystal structure (PDB ID: 2UUV) was imported into the Schrodinger software and processed as follows: Metal ions were removed; unsaturated atoms were hydrogenated; amino acid residues at the N and C termini were made neutral; and protein and original ligands were retained to remove atom and water molecule impurities. The OPLS_2005 position was selected to optimize protein structure and utilize sample water orientations as parameters to optimize hydrogen bonding.Ligand preparation utilized ChemBioDraw Ultra 11.0 in the ChemBioOffice 2010 to draw planar structures of the micromolecules, which were imported into ChemBio3D Ultra 11.0 for the generation of 3D structures, which were saved in mol2 format. The mol2fileswere then imported into Schrodinger Suite 2009 software and processed with the LigPrep module, complete desalting, add charge and produce ionization consistent with human body pH. The OPLS_2005 position was also selected for the optimized molecules to match that of the optimized acceptor. ADME parameters, namely oil-water partition coefficient (logPo/w), polarization surface area (PSA), water solubility (logS) and apparent Maden Darby Canine Kidney cell permeability (PMDCK), and toxicity factors, namely rodent carcinogenicity, mutagenicity, skin irritancy, ocular irritation and aerobic biodegradability, were subsequently simulated in the Schrodinger Suite 2009 software. […]

Pipeline specifications

Software tools QikProp, LigPrep
Applications Drug design, Protein structure analysis
Organisms Homo sapiens
Diseases Glioma, Metabolic Diseases, Neoplasms, Drug-Related Side Effects and Adverse Reactions