Molecular models obtained from structure-based docking rationalized the enzymatic data.
The second takeaway from these two studies is that for any structure-based docking model to be successful, multiple co-binding peptides will need to be considered when docking any drug of interest.
In this study, we are employing structure-based docking [38] to predict and analyze the molecular interactions between different drugs and the relatively common HLA-B*57 01 HLA-B*57 01
In the second case, a ligand-based screen would return molecules that resemble the structure-based docking hits.
We first used LBDS (Ligand-Based Docking System) and SBDS (Structure-Based Docking System) to develop the small-molecule Smac-mimetic IAP antagonist, which was designed to bind to the BIR3 domain of IAP family members, as well as EGFR.
In the past years, several computational methods have been used for virtual screening PXR's agonists, such as structure-based docking [ 18– 20], ligand-based QSAR [ 21, 22], machine learning [ 18, 23], and pharmacophore model [ 24, 25].
Such structural information would enhance the druggability value by facilitating a structure-based drug design strategy, including homology modeling, docking, virtual screening or pharmacophore-based screening [29], [30].
We utilised a structure-based strategy to select LLL-3 as a STA-21 structural analogue and docking simulation showed a similar binding mode as STA-21.
Structure-based molecular docking using Glide and the human VDR structure (PDB code 1S19): (a) Docking results for all compounds with their associated XP docking and eModel scores, mechanism and experimental AC50 values; (b) Binding modes of calcipotriol (red) and proflavine hydrochloride (blue) superimposed in the binding site.
Moreover, we applied structure-based 3D docking and molecular dynamics simulations to predict and analyze the binding modes of our experimental hits (including both agonists and antagonists).
We combined a ligand-based pharmacophore design with a structure-based protein/ligand docking using the software MOE in order to evaluate the underlying structure/activity relationship.
