Phakthanakanok Krongsakda, Ratanakhanokchai Khanok, Kyu Khin Lay, Sompornpisut Pornthep, Watts Aaron, Pinitglang Surapong
Division of Biochemical Technology, School of Bioresources and Technology, King Mongkut's University of Technology Thonburi, Bangkok, Thailand.
BMC Bioinformatics. 2009 Jan 30;10 Suppl 1(Suppl 1):S48. doi: 10.1186/1471-2105-10-S1-S48.
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.
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.
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.
严重急性呼吸综合征冠状病毒主要蛋白酶（SARS CoVMpro）是严重急性呼吸综合征病毒复制的一种重要酶。SARS CoVMpro的活性位点区域分为8个亚位点。了解SARS CoVMpro与特定底物的结合模式很有用，有助于基于结构的药物设计。本研究的目的是通过分子对接和分子动力学（MD）模拟方法，研究SARS CoVMpro与两种八肽之间的结合模式，特别是在S3亚位点区域。
SARS CoVMpro的单圈α-螺旋链（残基47-54）直接参与酶-底物复合物的诱导契合模型。由于存在Glu47，该酶的S3亚位点有一个带负电荷的区域。在MD模拟过程中，该酶的Glu47在与八肽的P3Lys静电结合中起关键作用。
对SARS CoVMpro-八肽复合物进行了MD模拟。该假设提出，SARS CoVMpro的Glu47是S3亚位点中的一个重要残基，参与与八肽的P3Lys结合。
