Bio Chem Press  Internet Electronic Journal of Molecular Design is a refereed journal for scientific papers regarding all applications of molecular design
Home | News | Current Issue | Journal Index | IECMD 2004 | Preprint Index | Instructions for Authors | Send the Manuscript | Special Issue
 BioChemPress.com  To bookmark this site press Ctrl D
 
   Home
   News & Announcements
  Journal Info
   Current Issue
   Journal Index
   Preprint Index
   Editor
   Advisory Board
  Conference Info
   IECMD 2004
   Day 1
   Day 2
   Day 3
   Day 4
   Day 5
   Day 6
   Day 7
   Day 8
   Day 9
   Day 10
   IECMD 2003
  BioChem Links
   CoEPrA
   Support Vector Machines
  Author Info
   Instructions for Authors
   Send the Manuscript
   Special Issue
  Contact
   Editorial Office
   Subscription
   Advertising
   Copyright
  User Info
   Terms of Use
   License

Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
ABSTRACT - Internet Electron. J. Mol. Des. May 2008, Volume 7, Number 5, 97-113

The Calcium Ion and Conserved Water Molecules in Neuraminidases: Roles and Implications for Substrate Binding
Gang Yang, Zhiwei Yang, Yuangang Zu, Xiaomin Wu, and Yujie Fu
Internet Electron. J. Mol. Des. 2008, 7, 97-113

Free: Download the paper in PDF format Return to Table of Contents Get Acrobat Reader to view and print the paper

Abstract:
Neuraminidases are essential to the replication of influenza virus by catalyzing the cleavage of the a-ketosidic connection between the sugar residue and the sialic acid. Our aim in this paper was to study the roles of the calcium ion and conserved water molecules played during the substrate bindings towards the N9 subtype neuraminidase. In addition, the interaction modes between substrates and receptors were predicted based on structural and property analyses, which were confirmed by docking results. Molecular mechanics and molecular docking simulations as well as density functional calculations were performed using InsightII 2005 and Gaussian 98 software packages. With the inclusion of the calcium ion, the neuraminidase active site is close in both size and shape to that of the crystal structure whereas shrunk severely in the absence of the calcium ion as confirmed by binding-site searching results. It was also found that the calcium ion or/and conserved water molecules cause the secondary structural transitions of the active site. As a result of structural transformations, the properties of the sub-regions in the active site are greatly altered. The molecular docking results are in good agreement with the above implications from structural and property analyses. The calcium ion is crucial to the maintenance of the active site of neuraminidase whereas the conserved water molecules exert a relatively small influence. The binding modes between substrates and receptors can be well predicted via structural and property analyses: sub-regions 1 and 3 (S1 and S3) are responsible for the locations of substrates whereas the orientations of substrates can be changed by sub-regions 2 and 4 (S2 and S4). Accordingly, the present results are useful to guide the substrate-receptor interaction studies and structure-based rational drug designs.

Free: Download the paper in PDF format Return to Table of Contents Get Acrobat Reader to view and print the paper

Home | News | Current Issue | Journal Index | IECMD 2004 | Preprint Index | Instructions for Authors | Send the Manuscript | Special Issue
Last changes: January 5, 2006 Webmaster
http://www.biochempress.com/
Copyright © 2001-2006 Ovidiu Ivanciuc