Evaluation of Advanced Structure-Based Virtual Screening Methods for Computer-Aided Drug Discovery

Computational virtual screening has become an essential platform of drug discovery for the efficient identification of active candidates. Moleculardocking, a key technology of receptor-centric virtual screening, is commonly used to predict the binding affinities of chemical compounds on target receptors. Despite the advancement and extensive application of these methods, substantial improvement is still required to increase their accuracy and time-efficiency. Here, we evaluate several advanced structure-based virtual screening approaches for elucidating the rank-order activity of chemical libraries, and the quantitative structureactivity relationship (QSAR). Our results show that the ensemble-average free energy estimation, including implicit solvation energy terms, significantly improves the hit enrichment of the virtual screening. We also demonstrate that the assignment of quantum mechanical-polarized (QM-polarized) partial charges to docked ligands contributes to the reproduction of the crystal pose of ligands in the docking and scoring procedure.

Development of Gentamicin Loaded PLGA Microspheres for the Treatment of Musculoskeletal Infection: In Vivo Evaluation / 대한정형외과연구학회지

PURPOSE: We evaluate in vitro and in vivo efficacy of newly developed gentamicin loaded PLGA microspheres for the treatment of musculoskeletal infection. MATERIALS AND METHODS: Controlled gentamicin sulfate releasing microspheres manufactured from biodegradable PLGA were prepared with an Oil/Oil solvent evaporation method for the treatment of musculoskeletal infection. The in vitro release amount of GS was analyzed by high performance liquid chromatography (HPLC) and the released GS activity was determined by microbiological assay using staphylococcus (S) aureus, respectively. The results of inhibition zone test agree well with the HPLC results obtained from the in vitro release test. RESULTS: The microspheres of different size were obtained with varying the experimental conditions, and the shape of microspheres was smooth and spherical. The PLGA microspheres release gentamicin for 67 days in in vitro test. There was significant inhibition around microphere PLGA from 1 day to 7th week in inhibition zone test The inhibition was reduced after 8th week. and there was no inhibition at 9th week PLGA microspheres. CONCLUSION: It can be suggested that GS/PLGA MSs implantable system that provided a prolonged delivery of GS was found to be effective against S. aureus infection for desired period.