roca pharmacophore-based virtual screening  (MolPort Inc)

Journal: Molecular Medicine

Article Title: Novel eIF4A1 inhibitors with anti‐tumor activity in lymphoma

doi: 10.1186/s10020-022-00534-0

Figure Lengend Snippet: Key interactions in the eIF4A1—RocA structure

Article Snippet: RocA pharmacophore-based virtual screening of the MolPort and ZINC15 databases was conducted using the Unity module of the Sybyl-X 2.1.1 suite using its ‘Flex Search’ option.

Techniques: Residue

Journal: Molecular Medicine

Article Title: Novel eIF4A1 inhibitors with anti‐tumor activity in lymphoma

doi: 10.1186/s10020-022-00534-0

Figure Lengend Snippet: Flow chart representing the process taken to identify new small molecule inhibitors for eIF4A. A Model of RocA used to define important pharmacophore features used in pharmacophore-based virtual screening experiment. In yellow circles are shown regions defining positioning of aromatic rings. The red circle indicates a hydrogen bond acceptor feature, while the blue circle indicates a hydrogen bond donor feature B Workflow for virtual screening strategy that identified RBF98 as the top hit. Stages for this workflow included obtaining the crystal structure of eIF4A1 complexed with RocA, scoring interactions between these two species, constructing and implementing the virtual screening pharmacophore, high-throughput molecular docking, energy minimizations of solutions, preliminary scoring of solutions in HINT, and final energy minimizations and scoring, followed by the purchase of the 29 top-scoring hits

Article Snippet: RocA pharmacophore-based virtual screening of the MolPort and ZINC15 databases was conducted using the Unity module of the Sybyl-X 2.1.1 suite using its ‘Flex Search’ option.

Techniques: High Throughput Screening Assay

Journal: Molecular Medicine

Article Title: Novel eIF4A1 inhibitors with anti‐tumor activity in lymphoma

doi: 10.1186/s10020-022-00534-0

Figure Lengend Snippet: Interaction differences between RocA and docked RBF98. A Interaction environments for RocA and RBF98. The above two panels show stick representations of the interactions made between RocA and RBF98 and their surrounding environments. Green, transparent ovals are used to two-dimensionally represent possible π-π stacking interactions between the ligands and surrounding residues. Dashed lines between the ligands and surrounding residues are used to indicate hydrogen bonding, where the color indicates the donor/acceptor character of the ligand atom (blue = donor; red = acceptor). B Summary of results from secondary screening of RBF98 analogues, purchased from MolPort. Boxes surrounding different moieties of RBF98 correspond by color to the larger boxes containing functional groups that were sampled as part of this secondary screen in different combinations

Article Snippet: RocA pharmacophore-based virtual screening of the MolPort and ZINC15 databases was conducted using the Unity module of the Sybyl-X 2.1.1 suite using its ‘Flex Search’ option.

Techniques: Analogues, Functional Assay