University of Oulu

Yadav, D., Kumar, S., Saloni, ., Misra, S., Yadav, L., Teli, M., Sharma, P., Chaudhary, S., Kumar, N., Choi, E., Kim, H., Kim, M. (2018) Molecular Insights into the Interaction of RONS and Thieno[3,2-c]pyran Analogs with SIRT6/COX-2: A Molecular Dynamics Study. Scientific Reports, 8, 4777. doi:10.1038/s41598-018-22972-9

Molecular insights into the interaction of RONS and thieno[3,2-c]pyran analogs with SIRT6/COX-2 : a molecular dynamics study

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Author: Yadav, Dharmendra K.1; Kumar, Surendra1; Saloni1;
Organizations: 1College of Pharmacy, Gachon University of Medicine and Science, 191, Hambangmoe-ro, Yeonsu-gu, Incheon, 21936, Republic of Korea
2Department of Biochemistry, All India Institute of Medical Science, Jodhpur, Rajasthan, 342005, India
3Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur, 302017, India
4Faculty of Biochemistry and Molecular Medicine Aapistie, University of Oulu, 7A, Oulu, 90220, Finland
5Plasma Bioscience Research Center/Department of Electrical and Biological Physics, Kwangwoon University, 20 Kwangwon-Ro, Nowon-Gu, Seoul, 139-701, Republic of Korea
6Present address: Department of Chemistry, Research group PLASMANT, University of Antwerp, BE-2610, Wilrijk-Antwerp, Belgium
7School of Pharmacy, Sungkyunkwan University, Suwon, 16419, Republic of Korea
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 4.4 MB)
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Language: English
Published: Springer Nature, 2018
Publish Date: 2018-04-16


SIRT6 and COX-2 are oncogenes target that promote the expression of proinflammatory and pro-survival proteins through a signaling pathway, which leads to increased survival and proliferation of tumor cells. However, COX-2 also suppresses skin tumorigenesis and their relationship with SIRT6, making it an interesting target for the discovery of drugs with anti-inflammatory and anti-cancer properties. Herein, we studied the interaction of thieno[3,2-c]pyran analogs and RONS species with SIRT6 and COX-2 through the use of molecular docking and molecular dynamic simulations. Molecular docking studies revealed the importance of hydrophobic and hydrophilic amino acid residues for the stability. The molecular dynamics study examined conformational changes in the enzymes caused by the binding of the substrates and how those changes affected the stability of the protein-drug complex. The average RMSD values of the backbone atoms in compounds 6 and 10 were calculated from 1000 ps to 10000 ps and were found to be 0.13 nm for both compounds. Similarly, the radius of gyration values for compounds 6 and 10 were found to be 1.87 ± 0.03 nm and 1.86 ± 0.02 nm, respectively. The work presented here, will be of great help in lead identification and optimization for early drug discovery.

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Series: Scientific reports
ISSN: 2045-2322
ISSN-E: 2045-2322
ISSN-L: 2045-2322
Volume: 8
Article number: 4777
DOI: 10.1038/s41598-018-22972-9
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This study was supported by the Basic Science Research Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science, and Technology (No.: 2017R1C1B2003380) at Gachon University of Medicine and Science, Incheon city, Korea and Science & Engineering Research Board (SERB), New Delhi (, for financial support as Young Scientist fellowship (No.: SB/YS/LS-130/2014) at the All India Institute of Medical Sciences, Jodhpur, India. SC acknowledges DST, New Delhi for DST-RFBR Indo-Russian Joint Research Project (INT/RUS/RFBR/P-169) and CSIR, New Delhi for EMR Grant [02(0189)/14/EMR-II]. Authors are thankful to The National Institute of Supercomputing and Network/Korea Institute of Science and Technology Information provided supercomputing resources including technical support (No. KSC-2017-C1-0013; KSC-2017-C2-0017) and NK acknowledges the Research Foundation-Flanders (FWO), grant numbers 12J5617N and Research group PLASMANT, Department of Chemistry, University of Antwerp, Antwerp, Belgium.
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