Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Discovery of HIV Type 1 Aspartic Protease Hit Compounds through Combined Computational Approaches
Δημιουργός/Συγγραφέας:	Xanthopoulos D. Kritsi E. Supuran C.T. [EL] Παπαδόπουλος, Μάνθος Γ.[EN] Papadopoulos, Manthos G. Leonis G. [EL] Ζουμπουλάκης, Παναγιώτης[EN] Zoumpoulakis, Panagiotis
Εκδότης:	John Wiley and Sons Ltd
Ημερομηνία:	2016
Γλώσσα:	Αγγλικά
ISSN:	1860-7179
DOI:	10.1002/cmdc.201600220
Άλλο:	PubMed ID: 27411556
Περίληψη:	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.
Τίτλος πηγής δημοσίευσης:	ChemMedChem
Σελίδες:	1646-1652
Θεματική Κατηγορία:	[EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	drug discovery HIV inhibitors molecular modeling proteases
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο