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Issue 84, 2015
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Protein–ligand interaction study of signal transducer smoothened protein with different drugs: molecular docking and QM/MM calculations

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Abstract

In this work, the interaction of signal transducer smoothened (SMO) protein, one of the main members of the Hedgehog (Hh) signaling pathway, with different ligands was studied. Seven hundred molecules, known as SMO ligands in literature, were selected for the docking screens. The site of the antitumor agent LY2940680, present in the X-ray crystal structure of the SMO protein, was selected as the binding site to study the interaction of the selected ligands with the protein. Docking screens only showed ten ligands that can be considered as favorable ligands based on their calculated free binding energies. The amino acid residues responsible for interacting with the ligands were identified. Quantum mechanics/molecular mechanics (QM/MM) calculations were also performed on the structure of the protein interacting with the favorable ligands to obtain more accurate results for their electronic interaction energies. The contribution of the van der Waals (vdW) and electrostatic interaction in the calculated electronic interaction energy of each ligand were calculated by QM/MM calculations. In addition, the effect of the polarization of the wave function of ligand in the active site of the protein on its electronic interaction with the protein was also studied.

Graphical abstract: Protein–ligand interaction study of signal transducer smoothened protein with different drugs: molecular docking and QM/MM calculations

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Publication details

The article was received on 08 May 2015, accepted on 30 Jul 2015 and first published on 30 Jul 2015


Article type: Paper
DOI: 10.1039/C5RA08609D
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Citation: RSC Adv., 2015,5, 68829-68838
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    Protein–ligand interaction study of signal transducer smoothened protein with different drugs: molecular docking and QM/MM calculations

    H. Farrokhpour, V. Pakatchian, A. Hajipour, F. Abyar, A. Najafi Chermahini and F. Fakhari, RSC Adv., 2015, 5, 68829
    DOI: 10.1039/C5RA08609D

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