title: A computational analysis of SARS cysteine proteinase-octapeptide substrate interaction: implication for structure and active site binding mechanism.
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 alpha-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.
authors.affiliation: Division of Biochemical Technology, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Bangkok, Thailand. s7500802@st.kmutt.ac.th
authors.forename: Krongsakda
authors.initials: K
authors.lastname: Phakthanakanok
authors.forename: Khanok
authors.initials: K
authors.lastname: Ratanakhanokchai
authors.forename: Khin Lay
authors.initials: KL
authors.lastname: Kyu
authors.forename: Pornthep
authors.initials: P
authors.lastname: Sompornpisut
authors.forename: Aaron
authors.initials: A
authors.lastname: Watts
authors.forename: Surapong
authors.initials: S
authors.lastname: Pinitglang
mesh_terms: D001665:Binding Sites; D020134:Catalytic Domain; D019295:Computational Biology / Q000379:methods*; D000086782:Coronavirus 3C Proteases; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation; D045473:Severe acute respiratory syndrome-related coronavirus / Q000201:enzymology* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D014764:Viral Proteins / Q000737:chemistry* / Q000378:metabolism
chemical_list: D015853:Cysteine Proteinase Inhibitors; D009842:Oligopeptides; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086782:Coronavirus 3C Proteases