Receptor-based virtual screening evaluation for the identification of estrogen receptorβligands

Abstract

In this paper, a receptor-based virtual screening study for the identification of estrogen receptor b (ERb) ligands was developed. Starting from a commercial database of 400 000 molecules, only six compounds resulted to be potential active ligands of ERb. Interestingly, all the six molecules possess scaffolds that had already been reported in known ERb ligands. Therefore, the results obtained herein confirm the reliability of our virtual screening procedure, thus encouraging the application of this protocol to larger commercial databases in order to identify new ERb ligands.

Application of MM-PBSA Methods in Virtual Screening

“…However, one of the main limitations of docking is related to the estimation of ligand-protein binding affinities, which are normally calculated by applying simple scoring functions on the predicted docking poses. The scoring step in docking calculations has a double scope: the evaluation and ranking of the different binding poses predicted for a single compound, in order to identify the most reliable one (which should be the top-scored), and the comparison of the binding poses predicted for different ligands, aimed at identifying the compounds that may establish strong interactions with the protein binding site and are thus more likely to actually bind to the target [2]. Both scopes are obviously important when performing docking evaluations, but when these are applied to VS studies, in which a large number of molecules are generally screened, the ranking of compounds based on their docking scores assumes a fundamental role in order to prioritize those that have more chances to be actual ligands of the target of interest, advance them to additional evaluation steps and eventually select the most promising ones for biological experiments assessing their activity.…”

Identification of a new STAT3 dimerization inhibitor through a pharmacophore-based virtual screening approach

“…The extra precision method (XP) of GLIDE software 23 proved to be a particularly reliable docking procedure, according to our previous cross-docking studies carried out on different protein targets 32,33 . For this reason, it was used as a first docking step to select the compounds that were more likely to bind the STAT3 SH2 domain by assuming a disposition matching the features of the pharmacophore model.…”

Binding investigation and preliminary optimisation of the 3-amino-1,2,4-triazin-5(2H)-one core for the development of new Fyn inhibitors

“…Nine different docking procedures were applied and for each docking calculation only the best scored pose was taken into account 23–25 . The docking calculations were carried out by using AUTODOCK 4.2.3 26 , DOCK 6.7 27 , FRED 3.0 28–31 , GOLD 5.1 (with the ASP, CSCORE and GSCORE scoring functions) 32 , GLIDE 5.0 (with the SP scoring function) 33 , AUTODOCK VINA 1.1 34 , and PLANTS 35 accordingly employing the procedures previously described 24 , 36 . The ligands were docked into the binding site of human Fyn (2DQ7 37 PDB code) by using the different docking procedures, then the root mean square deviation (RMSD) of each of these docking poses against the remaining docking results was evaluated using the rms_analysis software of the GOLD suite.…”