Molecular Docking and Molecular Dynamics Simulation of SARS Cysteine Proteinase in Complex with Its Specific Substrate

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Krongsakda Phakthanakanok
King Mongkut's University of Technology Thonburi, Thakham, Bangkuntien, Bangkok 10150
Khanok Ratanakhanokchai
King Mongkut's University of Technology Thonburi, Thakham, Bangkuntien, Bangkok 10150
Khin Lay Kyu
King Mongkut's University of Technology Thonburi, Thakham, Bangkuntien, Bangkok 10150
Pornthep Sompornpisut
Chulalongkorn University, Patumwan, Bangkok, 10330
Surapong Pinitglang
The University of the Thai Chamber of Commerce, Dindaeng, Bangkok 10400

Abstract

The coronavirus main cysteine proteinase (CoVMpro) is a key target for drug development againstsevere acute respiratory syndrome virus (SARS). The active site of the enzyme is large cleft which isdivided with several subsites. Subsites region, S5-S4-S3-S2-S1S1´-S2´-S3´ where accommodated withspecific octapeptide (P5Thr-P4Val-P3Lys-P2Leu-P1Gln-P1´Ala-P2´Gly-P3´Phe). The research is toinvestigate interaction between the enzyme and the octapeptide using molecular docking includingmolecular dynamics simulation. The results indicated that S3, S1 and S4´ should be critical subsites forspecific octapeptide binding. S3Glu47 specific to P3Lys with electrostatic interaction, S1 specific to P1Gln,including S4Thr-cluster (residues 21, 24-26 and 45) specific to octapeptide at C-terminal with hydrogenbonds. Several waters within 5 Å of octapeptide related to binding mode. Molecular dynamics simulationafter 500 ps indicated that protein chain of one turn α-helix was highly flexible and became to induced fitmodel in the latter.

Keywords : Cysteine Proteinase / Molecular Docking / Molecular Dynamics Simulation / SARS

Article Details

Issue
Vol. 31 No. 3 (2008): July - September
Section
Original Articles
Author Biographies

Krongsakda Phakthanakanok, King Mongkut's University of Technology Thonburi, Thakham, Bangkuntien, Bangkok 10150

Graduate Student, Division of Biochemical Technology, School of Bioresources and Technology.

Khanok Ratanakhanokchai, King Mongkut's University of Technology Thonburi, Thakham, Bangkuntien, Bangkok 10150

Associate Professor, Division of Biochemical Technology, School of Bioresources and Technology.

Khin Lay Kyu, King Mongkut's University of Technology Thonburi, Thakham, Bangkuntien, Bangkok 10150

Assistant Professor, Division of Biochemical Technology, School of Bioresources and Technology.

Pornthep Sompornpisut, Chulalongkorn University, Patumwan, Bangkok, 10330

Assistant Professor, Computational Chemistry Unit Cell, Department of Chemistry, Faculty of Science.

Surapong Pinitglang, The University of the Thai Chamber of Commerce, Dindaeng, Bangkok 10400

Assistant Professor, Department of Food Science and Technology, Faculty of Science.