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Pipeline publication

[…] 1JNQ with resolution of 2.10 Å) were retrieved from the Research Collaboratory for Structural Bioinformatics Protein Data Bank (PDB) (Anonymous, www.rcsb.org). A chain of all proteins (except for XO and COX-2, where C chain; mPGES-2, where A, B, C, and D chains; and tyrosinase, where A and B chains) was preprocessed separately by deleting other chains (B, C, and D), ligand, as well as the crystallographically observed water molecules (water without hydrogen bonds). All the proteins above mentioned were prepared using UCSF Chimera software (www.cgi.ucsf.edu/chimera) for Autodock 4.2, whereas in the case of CDOCKER inbuild protein preparation protocol (Accelrys, San Diego, USA) was adopted., Molinspiration online database was used for the two selected ligands to calculate thirteen descriptors (www.molinspiration.com) which are logP, polar surface area, molecular weight (MW), number of atoms, number of O or N, number of OH or NH, number of rotatable bonds, volume, drug-likeness including G-protein-coupled receptors ligand, ion channel modulator, kinase inhibitor, and nuclear receptor ligand, and the number of violations to Lipinski's rule., Both ADME and TOPKAT analyses were performed using Discovery Studio® 3.1 (Accelrys, San Diego, USA). ADME analysis was performed using six descriptors such as human intestinal absorption, aqueous solubility, blood–brain barrier, cytochrome P450 2D6, plasma protein binding, and hepatotoxicity. As for the TOPKAT analysis, five descriptors were used which includes aerobic biodegradability (AB), Ames mutagenicity, ocular irritancy, skin irritancy, and skin sensitization., Docking studies were performed on the protein crystal structures of COX-2, mPGES-2, tyrosinase, HNE, MMP-2, MMP-9, XO, SQS, NOS, and HAR obtained from PDB using the CDOCKER protocol under the protein–ligand interaction section in Discovery Studio® 3.1 (Accelrys, San Diego, USA). In general, CDOCKER is a grid-based molecular docking method that employs CHARMM force fields. Protein was first held rigid while the ligands were allowed to flex during the refinement. Two hundred random ligand conformations were then generated from the initial ligand structure through high-temperature molecular dynamics followed by random rotations, refinement by grid-based (GRID I) simulated annealing, and a final grid-based or full force field minimization.[] In this experiment, the ligand was heated to a temperature of 700 K in 2000 steps, and the cooling steps were set in 5000 steps to 300 K with the grid extension set to 10 Å. Hydrogen atoms were added to the structures, and all ionizable residues were set at their default protonation state at a neutral pH. […]

Pipeline specifications

Software tools Molinspiration, TOPKAT, CHARMM
Databases RCSB PDB
Organisms Homo sapiens
Diseases Sexually Transmitted Diseases, Viral, Retroviridae Infections, HIV Infections, Drug-Related Side Effects and Adverse Reactions
Chemicals Nitric Oxide, Oxides, Reactive Nitrogen Species, Sugar Alcohols, Inositol, Inositol Phosphates, Hydrocarbons, Acyclic, Terpenes, Xanthines, Heterocyclic Compounds, 2-Ring