help button home button Biophys. J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Biophys. J. BioFAST: First Published February 10, 2006. doi:10.1529/biophysj.105.068130
© 2006 by the Biophysical Society.

A more recent version of this article appeared on May 1, 2006.
This Article
Right arrow Full Text (Rapid PDF)
Right arrow Supplement
Right arrow All Versions of this Article:
biophysj.105.068130v1
90/9/3106    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Author home page(s):
Dimitrios Morikis
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhang, L.
Right arrow Articles by Morikis, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, L.
Right arrow Articles by Morikis, D.

BIOPHYSICAL THEORY AND MODELING

Immunophysical properties and prediction of activities for VCP and SPICE using molecular dynamics and electrostatics

Li Zhang 1 and Dimitrios Morikis 1*

1 University of California at Riverside

* To whom correspondence should be addressed. E-mail: dmorikis{at}engr.ucr.edu.

Submitted on June 7, 2005
Revised on July 30, 2005
Accepted on 18 January 2006


  Abstract
We present immunophysical modeling for VCP, SPICE, and three mutants using molecular dynamics (MD) simulations and Poisson-Boltzmann-type electrostatic calculations. VCP and SPICE are homologous viral proteins that control the complement system by imitating, structurally and functionally, natural regulators of complement activation. VCP and SPICE consist of four complement control protein (CCP) modules connected with short flexible loops. MD simulations demonstrate that the modules of VCP/SPICE and their mutants exhibit a high degree of spatial mobility, which is affected by mutations on the surfaces of the rather compact CCP modules. Electrostatic calculations using snapshots form the MD trajectories demonstrate variable spatial distribution of the electrostatic potentials, which suggest dynamic binding properties. We use covariance analysis to identify correlated modular oscillations. We also use electrostatic similarity indices to cluster proteins with common electrostatic and activity properties. Our results are compared with experimental data to form correlations between the overall positive electrostatic potential of VCP/SPICE with binding and activity. We show how these correlations can be used to predict binding and activity properties. This work is expected to be useful for understanding the function of native CCP-containing regulators of complement activation and receptors and for the design of anti-viral therapeutics and complement inhibitors.

Key Words: Poisson-Boltzmann, SPICE, VCP, complement system, electrostatic calculations, molecular dynamics simulations




This article has been cited by other articles:


Home page
 J. Immunol.Home page
M. K. Liszewski, P. Bertram, M. K. Leung, R. Hauhart, L. Zhang, and J. P. Atkinson
Smallpox Inhibitor of Complement Enzymes (SPICE): Regulation of Complement Activation on Cells and Mechanism of Its Cellular Attachment
J. Immunol., September 15, 2008; 181(6): 4199 - 4207.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
V. N. Yadav, K. Pyaram, J. Mullick, and A. Sahu
Identification of Hot Spots in the Variola Virus Complement Inhibitor (SPICE) for Human Complement Regulation
J. Virol., April 1, 2008; 82(7): 3283 - 3294.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. K. Singh, J. Mullick, J. Bernet, and A. Sahu
Functional Characterization of the Complement Control Protein Homolog of Herpesvirus Saimiri: ARG-118 IS CRITICAL FOR FACTOR I COFACTOR ACTIVITIES
J. Biol. Chem., August 11, 2006; 281(32): 23119 - 23128.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Copyright © 2006 by the Biophysical Society.