Journal of Molecular Modeling

, Volume 18, Issue 2, pp 501–514 | Cite as

In silico investigations of possible routes of assembly of ORF 3a from SARS-CoV

Original Paper
First Online:
Received:
Accepted:

Abstract

ORF 3a of human severe acute respiratory syndrome corona virus (SARS-CoV) has been identified as a 274 amino acid membrane protein. When expressed in Xenopus oocytes the protein forms channels. Based on bioinformatics approaches the topology has been identified to include three transmembrane domains (TMDs). Since structural models from experiments are still lacking, computational methods can be challenged to generate such models. In this study, a ‘sequential approach’ for the assembly is proposed in which the individual TMDs are assembled one by one. This protocol is compared with a concerted protocol in which all TMDs are assembled simultaneously. The role of the loops between the TMDs during assembly of the monomers into a bundle is investigated. Molecular dynamics simulations for 20 ns are performed as a short equilibration to assess the bundle stability in a lipid environment. The results suggest that bundles are likely with the second TMD facing the putative pore. All the putative bundles show water molecules trapped within the lumen of the pore with only occasional events of complete crossing.

Keywords

Docking Ion channel Membrane protein Molecular dynamics Protein assembly 3a of SARS-CoV 
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Notes

Acknowledgments

WBF acknowledges National Yang-Ming University, the government of Taiwan and the National Science Council of Taiwan (NSC) for financial support. Thanks to D. Willbold (Jülich, D) for valuable discussions. We thank the National Center for High-Performance Computing of Taiwan (www.nchc.org.tw) for providing computer time.

Supplementary material

894_2011_1092_Fig8_ESM.jpg (117 kb)
Suppl-Fig. 1

Potential energies (MOE) of the assemblies to generate the monomer Seq1: TMD3 and TMD2 displayed in respect to distance rotational angle_1, rotational angle_2, and tilt (a). Potential energies of the assemblies of (TMD3+TMD2) with TMD1 are shown as for (a) to form Seq1 (b). The structure used for further studies is marked by the arrow (JPEG 117 kb)

894_2011_1092_MOESM1_ESM.tif (17.1 mb)
High resolution image (TIFF 17523 kb)
894_2011_1092_Fig9_ESM.jpg (138 kb)
Suppl-Fig. 2

Potential energies of the assembled tetramers without loops. Values for generating all the sequences are shown in dependence of distance (left panels), rotational angles (middle) and tilt (right panels). The arrows indicate models T-Seq1 (I), T-Seq2 (II), T-Sim (III) (JPEG 137 kb)

894_2011_1092_MOESM2_ESM.tif (19.6 mb)
High resolution image (TIFF 20109 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Institute of Biophotonics, School of Biomedical Science and EngineeringNational Yang-Ming UniversityTaipeiTaiwan

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