A computational analysis of SARS cysteine proteinaseoctapeptide substrate interaction: implication for structure and active site binding mechanism
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.Conclusions: 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.
Krongsakda Phakthanakanok Khanok Ratanakhanokchai Khin Lay Kyu Pornthep Sompornpisut Aaron Watts Surapong Pinitglang
Division of Biochemical Technology, School of Bioresources and Technology,King Mongkuts University Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science,Chulalongkorn Univers School of Biosciences, The University of Exeter, Exeter, United Kingdom Department of Food Science and Technology, School of Science, University of the Thai Chamber of Comm
国际会议
The 7th Asia-Pacific Bioinformatics Conference(第七届亚太生物信息学大会)
北京
英文
548-555
2009-01-01（万方平台首次上网日期，不代表论文的发表时间）