Journal: Molecules

Article Title: Molecular Docking and Structure-Based Drug Design Strategies

doi: 10.3390/molecules200713384

Figure Lengend Snippet: Examples of conformational search algorithms.

Article Snippet: FlexX [ ] , Molegro Virtual Docker [ ] .

Techniques:

Journal: Microorganisms

Article Title: Human-Based Immune Responsive In Vitro Infection Models for Validation of Novel TLR4 Antagonists Identified by Computational Discovery

doi: 10.3390/microorganisms10020243

Figure Lengend Snippet: The computational procedure in this work includes the use of several methods or filters, one after another, in order to filter a large molecular database, Enamine, and find active compounds for the selected target, TLR4/MD2. (1) The first step is filtering by the number of rotatable bonds. There were 2 parallel filtrations: for molecules with 0–4 rotatable bonds (“group 1”) and molecules with 7–15 rotatable bonds (“group 2”). (2) The second step is filtering the resulting molecules of groups 1 and 2 from the previous step, by the applicability domain properties of the known active molecules: no. of donor atoms, no. of acceptor atoms, logP, and molecular weight. (3) The third step is filtering groups 1 and 2 from the previous step, with a pharmacophore model, which can be based on known ligands for the target or on a known crystal structure of the target. Specifically, group 1 was filtered only by a ligand-based pharmacophore model, while group 2 was filtered by a ligand-based, as well as a structure-based pharmacophore model. (4) The last step is filtering groups 1 and 2 from the previous step, by docking to TLR4/MD2 crystal structure (PDB code: 2Z65), using two docking programs: FRED and FlexX. The resulting molecules were then filtered by calculating solubility descriptors using three methods. The candidates that passed all of these filters were later examined in vitro to find whether they are indeed active on TLR4.

Article Snippet: Docking was performed by two different programs: FlexX in LeadIT [ ] (BioSolveIT, Sankt Augustin, Germany) and FRED [ ] (OpenEye Scientific Software, Santa Fe, NM, USA).

Techniques: Molecular Weight, Solubility, In Vitro