Accelrys discovery studio 3

A reference H1N1 NA structure (A/California/04/2009) for molecular docking analysis on NA binding to 15a was obtained from the Protein Data Bank (PDB) accession No. 3TI6, which showed 3D structures of the viral NA complexed with OSV-C (Vavricka et al., 2011 (link)). The CHARMM force field parameters were first assigned for the PR8 NA protein and the binding site was defined using the advanced Define and Edit Binding Site tools. Docking calculations were carried out using ligandfit software interfaced with Accelrys Discovery Studio 3.5 (Accelrys Software Inc., San Diego, CA) (Venkatachalam et al., 2003 (link)). In detail, the ligand 15a was loaded in the protein’s binding site to have low-energy conformations using the protocol ‘Generate Conformations’ in Discovery Studio 3.5. To verify the reliability of our simulation protocol, we performed self-docking analysis using OSV-C as a reference antiviral compound. Based on the parameters used for OSV-C, 15a was in silico docked to the OSV-C binding site within the PR8 NA protein.

Docking simulations of the
ethynylflavones with human P450s 1A1 and 1A2 were performed using
the LigandFit module in Accelrys Discovery Studio 3.5 (Accelrys, San
Diego, CA). The crystal structures of human cytochrome P450s 1A1 and
1A2 in complex with α-naphthoflavone (PDB ID: 4I8V and 2HI4) are available from
the Protein Data Bank (PDB).^{23 (link),24 (link)} For the crystal structure
of P450 1A1, subunit A was used for docking simulations. Water molecules
in the crystal structures were removed, and hydrogen atoms were added
to the P450 templates under the CHARMm force field. The 3D structures
of ethynylflavones were built using a 3D-sketcher module in Accelrys
Discovery Studio. Partial atomic charges were assigned to each atom
with the Gasteiger Charge method, and energy minimization of each
molecule was performed using the conjugate gradient method with CHARMm
force field. The minimization was terminated when the energy gradient
convergence criterion of 0.001 kcal/mol·Å was reached. To
explore the binding modes of the 3D-structures of ethynylflavones
to P450s 1A1 and 1A2, the docking program LigandFit was used to automatically
dock the ligands into the active site cavities of the enzymes. In
the docking process, the standard flexible docking protocol was performed.
Ten conformers of each molecule were automatically formed, which are
the best fit into the defined active site cavities.