NDLI: Covalent complexes of proteasome model with peptide aldehyde inhibitors MG132 and MG101: docking and molecular dynamics study

Content Provider	Springer Nature Link
Author	Zhang, Siwei Shi, Yawei Jin, Hongwei Liu, Zhenming Zhang, Liangren Zhang, Lihe
Copyright Year	2009
Abstract	20S proteasome plays a critical role in the regulation of several important cellular processes and has drawn extensive interest in the field of anti-tumor research. Peptide aldehydes can inhibit the 20S proteasome activity by covalently binding to the active site of the β subunits. In this work, covalent docking in conjunction with molecular dynamics (MD) simulation was used to explore the binding mode of MG132. Two conformations with the lowest docking energy were selected as the representative binding modes. One of the conformations was confirmed as a more reasonable binding mode by molecular dynamics simulations. The binding mode analysis revealed that a space demanding aromatic group with a short linker at the P4 site of the peptide aldehyde inhibitor would form favorable hydrophobic contacts with the neighboring subunit. A bulky substituent at the P2 position would also increase the binding stability by reducing water accessibility of the covalent bond. This study contributed to our understanding of the mechanism and structure-activity relationship of the peptide aldehyde inhibitors and may provide useful information for rational drug design.
Starting Page	1481
Ending Page	1490
Page Count	10
File Format	PDF
ISSN	16102940
Journal	Journal of Molecular Modeling
Volume Number	15
Issue Number	12
e-ISSN	09485023
Language	English
Publisher	Springer-Verlag
Publisher Date	2009-05-14
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Covalent docking Molecular dynamics Peptide aldehydes Proteasome Structure-activity relationship Computer Application in Life Sciences Life Sciences Health Informatics Molecular Medicine Biomedicine general Computer Applications in Chemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Physical and Theoretical Chemistry Computational Theory and Mathematics Catalysis Inorganic Chemistry Computer Science Applications

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