Homology Modeling and Conformational Epitope Prediction of Envelope Protein of Alkhumra Haemorrhagic Fever Virus
Abstract
Background: The aim of this study was to generate in silico 3D-structure of the envelope protein of AHFV using homology modeling method to further predict its conformational epitopes and help other studies to investigate itsstructural features using the model.
Methods: A 3D-structure prediction was developed for the envelope protein of Alkhumra haemorrhagic fever virus (AHFV), an emerging tick-borne flavivirus, based on a homology modeling method using M4T and Modweb
servers, as the 3D-structure of the protein is not available yet. Modeled proteins were validated using Modfold 4 server and their accuracies were calculated based on their RSMDs. Having the 3D predicted model with high quality, conformational epitopes were predicted using DiscoTope 2.0.
Results: Model generated by M4T was more acceptable than the Modweb-generated model. The global score and Pvalue calculated by Modfold 4 ensured that a certifiable model was generated by M4T, since its global score was almost near 1 which is the score for a high resolution X-ray crystallography structure. Furthermore, itsthe P-value was much lower than 0.001 which means that the model is completely acceptable. Having 0.46 Å rmsd, this model was shown to be highly accurate. Results from DiscoTope 2.0 showed 26 residues as epitopes, forming conformational epitopes of the modeled protein.
Conclusion: The predicted model and epitopes for envelope protein of AHFV can be used in several therapeutic and diagnostic approaches including peptide vaccine development, structure based drug design or diagnostic kit development in order to facilitate the time consuming experimental epitope mapping process.
Alzahrani AG, Al Shaiban HM, Al Mazroa MA, Al-Hayani O, Macneil A, Rollin PE, Memish ZA (2010) Alkhurma hemorrhagic fever in humans, Najran, Saudi Arabia. Emerg Infect Dis. 16:1882–1888.
Charrel RN, Zaki AM, Fakeeh M, Yousef AI, de Chesse R, Attoui H, de Lamballerie X (2005) Low diversity of Alkhurma hemorrhagic fever virus, Saudi Arabia,1994–1999. Emerg Infect Dis. 11: 683–688.
Chothia C, Lesk A M (1986) The relation be- tween the divergence of sequence and structure in proteins. EMBO J. 5: 823.
Eswar N, John B, Mirkovic N, Fiser A, Ilyin VA, Pieper U, Stuart AC, Marti-Renom MA, Madhusudhan MS, Yerkovich B (2003) Tools for comparative protein structure modeling and analysis. Nu- cleic Acids Res. 31: 3375–3380.
Fernandez-Fuentes N, Madrid-Aliste CJ, Rai BK, Fajardo JE, Fiser A (2007) M4T: a comparative protein structure model- ing server. Nucleic Acids Res. 35:363–368.
Guex N, Peitsch MC, Schwede T (2009) Automated comparative protein structure modeling with SWISS‐MODEL and Swiss‐PdbViewer: A historical perspective. Electrophoresis. 30: 162–173.
Haste Andersen P, Nielsen M, Lund O (2006) Prediction of residues in discontinuous B‐cell epitopes using protein 3D structures. Protein Sci. 15: 2558–2567.
Kaplan W, Littlejohn TG (2001) Swiss-PDB viewer (deep view). Brief Bioinform. 2:195–197.
King AM, Adams MJ, Lefkowitz EJ, Carstens EB (2011) Virus taxonomy: IXth re- port of the International Committee on Taxonomy of Viruses. Vol 9. Elsevier.
Kringelum JV, Lundegaard C, Lund O, Nielsen M (2012) Reliable B cell epitope pre- dictions: impacts of method develop- ment and improved benchmarking. PLoS Comput Biol. 8: e1002829.
Liang L, Huang P, Wen M, Ni H, Tan S, Zhang Y, Chen Q (2012) Epitope peptides of influenza H3N2 virus neuraminidase gene designed by immunoinformatics. Acta Biochim Biophys Sinica. 44: 113–118.
Liang S, Zheng D, Standley D, Yao B, Zacharias M, Zhang C (2010) EPSVR and EPMeta: prediction of antigenic epitopes using support vector regres sion and multiple server results. BMC bioinformatics. 11: 381.
Madani TA (2005) Alkhumra virus infec- tion, a new viral hemorrhagic fever in Saudi Arabia. J Infect. 51: 91–97.
Madani TA, Azhar EI, Abuelzein el TM, Kao M, Al-Bar HM, Abu-Araki H, Niedrig M, Ksiazek TG (2011) Alkhumra (Alkhurma) virus outbreak in Najran, Saudi Arabia: epidemiological, clini- cal, and laboratory characteristics. J Infect. 62: 67–76.
Madani TA, Azhar EI, Abuelzein E-T, Kao M, Al-Bar HM, Niedrig M, Ksiazek TG (2012) Alkhumra, not Alkhurma, is the correct name of the new hemor- rhagic fever flavivirus identified in Saudi Arabia. Intervirology. 55: 259–260.
Maiorov VN, Crippen GM (1994) Signifi- cance of root-mean-square deviation in comparing three-dimensional structures of globular proteins. J Mol Biol. 235:625–634.
McGuffin LJ, Buenavista MT, Roche DB (2013) The ModFOLD4 server for the quality assessment of 3D protein mod- els. Nucleic Acids Res. 41: W368– W372.
Memish ZA, Charrel RN, Zaki AM, Fagbo SF (2010) Alkhurma haemorrhagic fever--a viral haemorrhagic disease unique to the Arabian Peninsula. Int J Antimicrob Agents. 36(1): 53–57.
Memish ZA, Fagbo SF, Assiri AM, Rollin P, Zaki AM, Charrel R, Mores C, MacNeil A (2012) Alkhurma viral hemorrhagic fever virus: proposed guidelines for de- tection, prevention, and control in Saudi Arabia. PLoS Negl Trop Dis. 6: e1604.
Mohabatkar H (2007) Prediction of epitopes and structural properties of Iranian HPV-16 E6 by bioinformatics meth- ods. Asian Pac J Cancer Prev. 8: 602–606.
Mohabatkar H, Mohsenzadeh S (2009) Bio- informatics Comparison of G Protein of Isfahan Virus with the Same Proteins of Two Other Closely Related Viruses of the Genus Vesiculovirus. Protein Pept Lett. 16: 1017–1023.
Mohabatkar H (2011) Computer-based com- parison of structural features of enve- lope protein of Alkhurma hemorrhagic fever virus with the homologous pro- teins of two closest viruses. Protein Pept Lett. 18: 559–567.
Mohabatkar H, Keyhanfar M, Behbahani M (2012) Protein bioinformatics applied to virology. Curr Protein Pept Sci. 13:547–559.
Pal D, Chakrabarti P (2002) On residues in the disallowed region of the Ramachandran map. Biopolymers. 63: 195–206.
Pastorino BA, Peyrefitte CN, Grandadam M, Thill MC, Tolou HJ, Bessaud M (2006) Mutagenesis analysis of the NS2B de- terminants of the Alkhurma virus NS2B- NS3 protease activation. J Gen Virol.
: 3279–3283.
Ponomarenko J, Bui H-H, Li W, Fusseder N, Bourne PE, Sette A, Peters B (2008) ElliPro: a new structure-based tool for the prediction of antibody epitopes. BMC bioinformatics. 9: 514.
Rey FA, Heinz FX, Mandl C, Kunz C, Harrison SC (1995) The envelope glycoprotein from tick-borne encephalitis virus at 2 Å resolution. Nature. 1995 May 25. 375(6529): 291–298.
Sun J, Wu D, Xu T, Wang X, Xu X, Tao L, Li Y, Cao Z-W (2009) SEPPA: a computational server for spatial epitope prediction of protein antigens. Nucleic Acids Res. 37: W612–W616.
Sweredoski MJ, Baldi P (2008) PEPITO: improved discontinuous B-cell epitope prediction using multiple distance thresh- olds and half sphere exposure. Bio- informatics. 24: 1459–1460
Wu KP, Wu CW, Tsao YP, Kuo TW, Lou YC, Lin CW, Cheng JW (2003) Struc- tural Basis of a Flavivirus Recognized by Its Neutralizing Antibody solution structure of the domain iii of the japanese encephalitis virus envelope protein. J Biol Chem. 278: 46007–46013.
Yasser E-M, Honavar V (2010) Recent ad- vances in B-cell epitope prediction methods. Immunome Res. 6: S2.
Zhu K, Day T, Warshaviak D, Murrett C, Friesner R, Pearlman D (2014) Anti- body Structure Determination Using a Combin’ation of Homology Modeling,Energy‐Based Refinement and Loop Prediction. Proteins: Struct, Funct, Bioinf.In press.
| Files | ||
| Issue | Vol 9 No 1 (2015) | |
| Section | Short Communication | |
| Keywords | ||
| 3D structure Homology modeling Conformational epitope Alkhumra haemorrhagic fever virus Envelope protein. | ||
| Rights and permissions | |
|
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
