Ab initio fragment molecular orbital study of molecular interactions in liganded retinoid X receptor: specification of residues associated with ligand inducible information transmission

The Journal of Physical Chemistry. B
Mika ItoShigenori Tanaka

Abstract

The ab initio fragment molecular orbital calculations were performed for the alpha-subtype of the human retinoid X receptor (hRXRalpha) complex with its natural ligand 9- cis retinoic acid (9cRA) to quantitatively specify the key residues with important roles for the ligand inducible information transmission of RXR. In the RXR-9cRA complex, the transactivation helix 12 (H12) adopts a canonical agonist conformation, which just corresponds to the transcriptional activation function 2 activating domain core (AF2C). Through the analyses of molecular interactions by the second-order Møller-Plesset perturbation (MP2) method, it was proved that Trp305 and Leu436 of the AF2C binding pocket would be important for the stabilization of the H12 canonical agonist conformation, and, at the same time, for the recognition of the 9cRA molecule. Besides, through the analyses of orbital interactions by the local MP2 (LMP2) method, it was found that Trp305 and Leu436 would recognize the 9cRA molecule especially at its C19 methyl group, which has been most notably targeted to modify for agonist and antagonist design. Moreover, on the basis of the relationships of molecular interactions, it was suggested that the interactions of Trp305 and Leu436 wi...Continue Reading

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Citations

Aug 27, 2011·Chemical Reviews·Mark S GordonLyudmila V Slipchenko
Mar 14, 2012·Physical Chemistry Chemical Physics : PCCP·Dmitri G FedorovKazuo Kitaura
Apr 18, 2014·Physical Chemistry Chemical Physics : PCCP·Shigenori TanakaKaori Fukuzawa
May 6, 2014·Journal of Molecular Graphics & Modelling·Akisumi OkamotoNoriyuki Kurita
Oct 25, 2011·Biochimica Et Biophysica Acta·Marcia I Dawson, Zebin Xia
Sep 27, 2014·Journal of Molecular Graphics & Modelling·Takeru MurakawaNoriyuki Kurita
Oct 1, 2010·Drug Discovery Today. Technologies
Mar 27, 2015·Chemical Society Reviews·Maximillian J S PhippsChris-Kriton Skylaris
May 2, 2009·Journal of Computational Chemistry·Takeshi IshikawaKazuo Kuwata
Sep 26, 2012·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Yosuke Suzuki, Shigenori Tanaka
Jan 9, 2009·The Journal of Physical Chemistry. B·Naoki TaguchiShigenori Tanaka
Feb 9, 2010·Journal of Chemical Theory and Computation·Takeshi Ishikawa, Kazuo Kuwata

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