Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Antihypertensive Drug Valsartan in Solution and at the AT(1) Receptor: Conformational Analysis, Dynamic NMR Spectroscopy, in Silico Docking, and Molecular Dynamics Simulations
Δημιουργός/Συγγραφέας:	Potamitis, Constantinos [EL] Ζερβού, Μαρία[EN] Zervou, Maria Katsiaras, Vassilis [EL] Ζουμπουλάκης, Παναγιώτης[EN] Zoumpoulakis, Panagiotis Durdagi, Serdar [EL] Παπαδόπουλος, Μάνθος Γ.[EN] Papadopoulos, Manthos G. Hayes, Joseph M. Grdadolnik, Simona Golic Kyrikou, Ioanna Argyropoulos, Dinutris Vatougia, Georgia [EL] Μαυρομούστακος, Θωμάς[EN] Mavromoustakos, Thomas
Εκδότης:	American Chemical Society
Τόπος έκδοσης:	Washington
Ημερομηνία:	2009-03
Γλώσσα:	Αγγλικά
ISSN:	1549-9596
DOI:	10.1021/ci800427s
Περίληψη:	The conformational properties of AT, antagonist valsartan have been analyzed both in solution and at the binding site of the receptor. Low energy conformations of valsartan in solution were explored by NMR spectroscopy and molecular modeling studies. The NMR results showed the existence of two distinct and almost isoenergetic conformations for valsartan (cis: trans ratio around the amide bond similar to 40:60) that coalesce at the temperature range of 55-60 degrees C in agreement with previous in solution conformational analysis study (Fang et al. Magn. Reson. Chem. 2007, 45, 929-936). Quantum mechanics and ONIOM calculations revealed that the bulky valsartan substituents actually contribute to stabilization of the transition state for interconversion. In silico docking and Molecular Dynamic studies were applied to study binding of valsartan at the AT, receptor site models, explicitly solvated and embedded in lipid bilayers and solvent molecules. These studies revealed that the majority of docked poses adopted a trans (major) conformation. Of paramount and maybe biological importance are the MD simulations results which showed that the two acidic groups of valsartan are bridged through LYS199 enabling it for multiple hydrogen bond interactions. In a lipid bilayer environment these interactions are enhanced, designating the important role of lipid bilayers for the better binding of valsartan and its stabilization at the active site.
Τίτλος πηγής δημοσίευσης:	Journal of Chemical Information and Modeling
Τόμος/Κεφάλαιο:	49
Τεύχος:	3
Σελίδες:	726-739
Θεματική Κατηγορία:	[EL] Χημεία (Γενικά)[EN] Chemistry (General) [EL] Ηλεκτρονικοί υπολογιστές. Επιστήμη των υπολογιστών[EN] Electronic computers. Computer science
Λέξεις-Κλειδιά:	Chemistry, Multidisciplinary Computer Science, Information Systems Computer Science, Interdisciplinary Applications
Αξιολόγηση από ομότιμους (peer reviewed):	Ναι
Κάτοχος πνευματικών δικαιωμάτων:	© AMER CHEMICAL SOC
ΙΒΦΧΒ: αρχειακή συλλογή:	Ινστιτούτο Οργανικής και Φαρμακευτικής Χημείας (ΙΟΦΧ) (έως 2012)
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο