Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2006 Oct 12:7:451.
doi: 10.1186/1471-2105-7-451.

MIMOX: a web tool for phage display based epitope mapping

Jian Huang  1 , Alex Gutteridge, Wataru Honda, Minoru Kanehisa
Affiliations

MIMOX: a web tool for phage display based epitope mapping

Jian Huang et al. BMC Bioinformatics. .

Abstract

Background: Phage display is widely used in basic research such as the exploration of protein-protein interaction sites and networks, and applied research such as the development of new drugs, vaccines, and diagnostics. It has also become a promising method for epitope mapping. Research on new algorithms that assist and automate phage display based epitope mapping has attracted many groups. Most of the existing tools have not been implemented as an online service until now however, making it less convenient for the community to access, utilize, and evaluate them.

Results: We present MIMOX, a free web tool that helps to map the native epitope of an antibody based on one or more user supplied mimotopes and the antigen structure. MIMOX was coded in Perl using modules from the Bioperl project. It has two sections. In the first section, MIMOX provides a simple interface for ClustalW to align a set of mimotopes. It also provides a simple statistical method to derive the consensus sequence and embeds JalView as a Java applet to view and manage the alignment. In the second section, MIMOX can map a single mimotope or a consensus sequence of a set of mimotopes, on to the corresponding antigen structure and search for all of the clusters of residues that could represent the native epitope. NACCESS is used to evaluate the surface accessibility of the candidate clusters; and Jmol is embedded to view them interactively in their 3D context. Initial case studies show that MIMOX can reproduce mappings from existing tools such as FINDMAP and 3DEX, as well as providing novel, rational results.

Conclusion: A web-based tool called MIMOX has been developed for phage display based epitope mapping. As a publicly available online service in this area, it is convenient for the community to access, utilize, and evaluate, complementing other existing programs. MIMOX is freely available at http://web.kuicr.kyoto-u.ac.jp/~hjian/mimox.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Overall architecture of MIMOX. MIMOX has two sections. The first section has 3 perl scripts. The script mimosa.pl aligns a set of mimotope sequences powered by ClustalW. The script jalviews.pl wraps JalView to view and manage the alignment. The script mimocs.pl derives a consensus sequence from the alignment. The second section also has 3 perl scripts. The script mimox.pl maps the user supplied sequence on to the given antigen structure and utilizes NACCESS to calculate the accessibility. The script parsa.pl displays the detailed accessibility information of each mapping result. The script jmol.pl wraps Jmol to view the mapping result interactively on the antigen structure.
Figure 2
Figure 2
Web interface of MIMOX section 1. Mimotopes selected out with trastuzumab[10] are input and aligned with wrapped ClustalW. The frequency of a given amino acid at each position of the alignment is calculated and displayed in a table. A 3D bar figure is also created, where the X axis represents the 20 amino acid types and gap, Y axis is the frequency and Z axis stands for the position of the aligned sequences. A consensus sequence is then suggested, which can be used in further mapping with MIMOX. The alignment can also be managed with the embedded JalView[20].
Figure 3
Figure 3
Web interface of MIMOX section 2. LLTTNKD[14] is mapped to the HIV gp120 envelope glycoprotein via MIMOX. When picking candidate residues in conservative mode and all other parameters in defaults, a new top result is suggested. The detailed accessibility data and the image of the new mapping result are dispaleyed accordingly.
Figure 4
Figure 4
Comparison of three mapping results. MIMOX was used to map LLTTNKD to HIV gp120 with three different methods. The top result using the default parameters is shown in image A. It is composed of the residues: L452 L453 T283 T455 N280 K282 D279 and has a 265.82 Å2 solvent accessible surface. The top result from conservative mode is shown in image B. It is composed of the residues: I360 I467 S465 T358 N356 K357 E464, with a 399.28 Å2 surface area. Image C shows the top result from the all heavy atoms method. It is composed of the residues: L86 V85 T244 S243 N229 K231 E267 and has an even larger accessible surface area of 562.89 Å2.
See this image and copyright information in PMC

References

    1. Smith GP. Filamentous fusion phage: novel expression vectors that display cloned antigens on the virion surface. Science. 1985;228:1315–1317. doi: 10.1126/science.4001944. - DOI - PubMed
    1. Scott JK, Smith GP. Searching for peptide ligands with an epitope library. Science. 1990;249:386–390. doi: 10.1126/science.1696028. - DOI - PubMed
    1. Smith GP, Petrenko VA. Phage Display. Chem Rev. 1997;97:391–410. doi: 10.1021/cr960065d. - DOI - PubMed
    1. Tong AH, Drees B, Nardelli G, Bader GD, Brannetti B, Castagnoli L, Evangelista M, Ferracuti S, Nelson B, Paoluzi S, et al. A combined experimental and computational strategy to define protein interaction networks for peptide recognition modules. Science. 2002;295:321–324. doi: 10.1126/science.1064987. - DOI - PubMed
    1. Thom G, Cockroft AC, Buchanan AG, Candotti CJ, Cohen ES, Lowne D, Monk P, Shorrock-Hart CP, Jermutus L, Minter RR. Probing a protein-protein interaction by in vitro evolution. Proc Natl Acad Sci USA. 2006;103:7619–7624. doi: 10.1073/pnas.0602341103. - DOI - PMC - PubMed

Publication types

Substances