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This article is part of the supplement: Selected papers from the Seventh Asia-Pacific Bioinformatics Conference (APBC 2009)

Open Access Research

A computational analysis of SARS cysteine proteinase-octapeptide substrate interaction: implication for structure and active site binding mechanism

Krongsakda Phakthanakanok1, Khanok Ratanakhanokchai1, Khin Lay Kyu1, Pornthep Sompornpisut2, Aaron Watts35 and Surapong Pinitglang4*

Author Affiliations

1 Division of Biochemical Technology, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Bangkok, Thailand

2 Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand

3 School of Biosciences, The University of Exeter, Exeter, UK

4 Department of Food Science and Technology, School of Science, University of the Thai Chamber of Commerce, Bangkok, Thailand

5 INTO University of Exeter, The Old Library, Exeter, UK

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BMC Bioinformatics 2009, 10(Suppl 1):S48  doi:10.1186/1471-2105-10-S1-S48

Published: 30 January 2009

Abstract

Background

SARS coronavirus main proteinase (SARS CoVMpro) is an important enzyme for the replication of Severe Acute Respiratory Syndrome virus. The active site region of SARS CoVMpro is divided into 8 subsites. Understanding the binding mode of SARS CoVMpro with a specific substrate is useful and contributes to structural-based drug design. The purpose of this research is to investigate the binding mode between the SARS CoVMpro and two octapeptides, especially in the region of the S3 subsite, through a molecular docking and molecular dynamics (MD) simulation approach.

Results

The one turn α-helix chain (residues 47–54) of the SARS CoVMpro was directly involved in the induced-fit model of the enzyme-substrate complex. The S3 subsite of the enzyme had a negatively charged region due to the presence of Glu47. During MD simulations, Glu47 of the enzyme was shown to play a key role in electrostatic bonding with the P3Lys of the octapeptide.

Conclusion

MD simulations were carried out on the SARS CoVMpro-octapeptide complex. The hypothesis proposed that Glu47 of SARS CoVMpro is an important residue in the S3 subsite and is involved in binding with P3Lys of the octapeptide.