TCP: a tool for designing chimera proteins based on the tertiary structure information

Takashi Yoneya,Reina Nishida

doi:10.1186/1471-2105-10-9

Abstract

BackgroundChimera proteins are widely used for the analysis of the protein-protein interaction region. One of the major issues is the epitope analysis of the monoclonal antibody. In the analysis, a continuous portion of an antigen is sequentially substituted into a different sequence. This method works well for an antibody recognizing a linear epitope, but not for that recognizing a discontinuous epitope. Although the designing the chimera proteins based on the tertiary structure information is required in such situations, there is no appropriate tool so far.ResultsIn light of the problem, we developed a tool named TCP (standing for a Tool for designing Chimera Proteins), which extracts some sets of mutually orthogonal cutting surfaces for designing chimera proteins using a genetic algorithm. TCP can also incorporate and consider the solvent accessible surface area information calculated by a DSSP program. The test results of our method indicate that the TCP is robust and applicable to various shapes of proteins.ConclusionWe developed TCP, a tool for designing chimera proteins based on the tertiary structure information. TCP is robust and possesses several favourable features, and we believe it is a useful tool for designing chimera proteins. TCP is freely available as an additional file of this manuscript for academic and non-profit organization.

Highlights

Chimera proteins are widely used for the analysis of the protein-protein interaction region
The chimera proteins should be designed based on the 3D structure information for the monoclonal antibodies which recognize discontinuous epitopes, there is no such a tool so far. In light of this problem, we developed a tool named TCP for designing chimera proteins based on the tertiary structure information
It is noteworthy that 1EVT:C and 1TNR:R were almost divided in spite of the elongated shapes

Summary

Introduction

Chimera proteins are widely used for the analysis of the protein-protein interaction region. A continuous portion of an antigen is sequentially substituted into a different sequence. This method works well for an antibody recognizing a linear epitope, but not for that recognizing a discontinuous epitope. The prediction of the epitopes in silico is convenient and various algorithms are developed so far Most of these programs use primary sequence information and properties of amino acid residues [1,2,3,4,5,6], and they are applicable to the prediction of the continuous linear epitopes. Many useful antibodies recognize tertiary structures, i.e. the discontinuous epitopes, and algorithms which predict the discontinuous ones are required. The phage clones in the library which have high affinities for the antibody of interest are selected and concentrated iter-

Methods

Results

Discussion

Conclusion