help button home button Biophys. J.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
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 reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Speelman, B.
Right arrow Articles by Post, C. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Speelman, B.
Right arrow Articles by Post, C. B.

Biophys J, January 2001, p. 121-129, Vol. 80, No. 1

Molecular Dynamics Simulations of Human Rhinovirus and an Antiviral Compound

Brent Speelman, Bernard R. Brooks,§ and Carol Beth Post

 Department of Medicinal Chemistry and Molecular Pharmacology, Purdue University, West Lafayette, Indiana 47907-1333; and  §Computational Biophysics Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 USA

The human rhinovirus 14 (HRV14) protomer, with or without the antiviral compound WIN 52084s, was simulated using molecular dynamics and rotational symmetry boundary conditions to model the effect of the entire icosahedral capsid. The protein asymmetrical unit, comprising four capsid proteins (VP1, VP2, VP3, and VP4) and two calcium ions, was solvated both on the exterior and the interior to fill the inside of the capsid. The stability of the simulations of this large system (~800 residues and 6,650 water molecules) is comparable to more conventional globular protein simulations. The influence of the antiviral compound on compressibility and positional fluctuations is reported. The compressibility, estimated from the density fluctuations in the region of the binding pocket, was found to be greater with WIN 52084s bound than without the drug, substantiating previous computations on reduced viral systems. An increase in compressibility correlates with an entropically more favorable system. In contrast to the increase in density fluctuations and compressibility, the positional fluctuations decreased dramatically for the external loops of VP1 and the N-terminus of VP3 when WIN 52084s is bound. Most of these VP1 and VP3 loops are found near the fivefold axis, a region whose mobility was not considered in reduced systems, but can be observed with this simulation of the full viral protomer. Altered loop flexibility is consistent with changes in proteolytic sensitivity observed experimentally. Moreover, decreased flexibility in these intraprotomeric loops is noteworthy since the externalization of VP4, part of VP1, and RNA during the uncoating process is thought to involve areas near the fivefold axis. Both the decrease in positional fluctuations at the fivefold axis and the increase in compressibility near the WIN pocket are discussed in relationship to the antiviral activity of stabilizing the virus against uncoating.

Biophys J, January 2001, p. 121-129, Vol. 80, No. 1
© 2001 by the Biophysical Society   0006-3495/01/01/121/09  $2.00


This article has been cited by other articles:


Home page
 Protein Sci.Home page
L. Wang and D. L. Smith
Capsid structure and dynamics of a human rhinovirus probed by hydrogen exchange mass spectrometry
Protein Sci., June 1, 2005; 14(6): 1661 - 1672.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
Y. Li, Z. Zhou, and C. B. Post
From the Cover: Dissociation of an antiviral compound from the internal pocket of human rhinovirus 14 capsid
PNAS, May 24, 2005; 102(21): 7529 - 7534.
[Abstract] [Full Text] [PDF]

Home page
 J. Virol.Home page
S. K. Tsang, B. M. McDermott, V. R. Racaniello, and J. M. Hogle
Kinetic Analysis of the Effect of Poliovirus Receptor on Viral Uncoating: the Receptor as a Catalyst
J. Virol., June 1, 2001; 75(11): 4984 - 4989.
[Abstract] [Full Text]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2001 by the Biophysical Society.