Please use this identifier to cite or link to this item:

Title: Conformational landscape and low lying excited states of imatinib
Authors: Vinteler, Emil
Stan, Nicoleta-Florina
Luchian, Raluca
Cainap, Calin
Ramalho, João P. Prates
Chis, Vasile
Issue Date: 2015
Citation: Vinteler, Emil; Stan, Nicoleta-Florina; Luchian, Raluca; Cainap, Calin; Ramalho, João P. Prates; Chis, Vasile. Conformational landscape and low lying excited states of imatinib, Journal of Molecular Modeling, 21, 4, 1-13, 2015.
Abstract: Abstract The conformational changes of imatinib (IMT) are crucial for understanding the ligand–receptor interaction and its mechanism of action [Agofonov et al. (2014) Nature Struct Mol Biol 21:848–853]. Therefore, here we investigated the free energy conformational landscape of the free IMT base, aiming to describe the three-dimensional structures and energetic stability of its conformers. Forty-five unique conformers, within an energy window of 4.8 kcal mol−1 were identified by a conformational search in gas-phase, at the B3LYP/6-31G(d) theoretical level. Among these, the 20most stable, as well as 4 conformers resulting from optimization of experimental structures found in the two known polymorphs of IMTand in the c- Abl complex were further refined using the 6-31+G(d,p) basis set and the polarizable continuum solvation model. The most stable conformers in gas-phase and water exhibit a V-shaped structure. The major difference between the most stable free conformers and the bioactive conformers consists in the relative orientation of the pyrimidine–pyridine groups responsible for hydrogen bonding interactions in the ATP-binding pocket. The ratio of mole fractions corresponding to the two known (α and β) polymorphic forms of IMT was estimated from the calculated thermochemical data, in quantitative agreement with the existing experimental data related to their solubility. The electronic absorption spectrum of this compound was investigated in water and explained based on the theoretical TD-DFT results, considering the Boltzmann populationaveraged computed data at CAM-B3LYP/6-31+G(d,p) level of theory for the nine most stable conformers.
Other Identifiers: 1610-2940
Type: article
Appears in Collections:CQE - Publicações - Artigos em Revistas Internacionais Com Arbitragem Científica

Files in This Item:

File Description SizeFormat
JMolMod_2015.pdf868.11 kBAdobe PDFView/Open
FacebookTwitterDeliciousLinkedInDiggGoogle BookmarksMySpaceOrkut
Formato BibTex mendeley Endnote Logotipo do DeGóis 

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.


Dspace Dspace
DSpace Software, version 1.6.2 Copyright © 2002-2008 MIT and Hewlett-Packard - Feedback
UEvora B-On Curriculum DeGois