@article{Xanthopoulos D._Kritsi E._Supuran C.T._ Papadopoulos M.G._Leonis G._ Zoumpoulakis P._2016, title={Discovery of HIV Type 1 Aspartic Protease Hit Compounds through Combined Computational Approaches}, ISSN={1860-7179}, archiveLocation={Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο}, url={https://hdl.handle.net/10442/17506}, DOI={10.1002/cmdc.201600220}, abstractNote={A combination of computational techniques and inhibition assay experiments was employed to identify hit compounds from commercial libraries with enhanced inhibitory potency against HIV type 1 aspartic protease (HIV PR). Extensive virtual screening with the aid of reliable pharmacophore models yielded five candidate protease inhibitors. Subsequent molecular dynamics and molecular mechanics Poisson–Boltzmann surface area free-energy calculations for the five ligand–HIV PR complexes suggested a high stability of the systems through hydrogen-bond interactions between the ligands and the protease’s flaps (Ile50/50′), as well as interactions with residues of the active site (Asp25/25′/29/29′/30/30′). Binding-energy calculations for the three most promising compounds yielded values between −5 and −10 kcal mol−1and suggested that van der Waals interactions contribute most favorably to the total energy. The predicted binding-energy values were verified by in vitro inhibition assays, which showed promising results in the high nanomolar range. These results provide structural considerations that may guide further hit-to-lead optimization toward improved anti-HIV drugs.}, journal={ChemMedChem}, publisher={John Wiley and Sons Ltd}, author={Xanthopoulos D. and Kritsi E. and Supuran C.T. and Papadopoulos M.G. and Leonis G. and Zoumpoulakis P.}, year={2016}, pages={1646–1652} }