Hsin-Wei Wang, Wei-Kuo Wu, Tun-Wen Pai, Yi-Ping Phoebe Chen, and Margaret Dah-Tsyr Chang
Unbound/Bound Antigen, Epitope Variation, Conformational Change, Conformational Epitope, Secondary Structure Element
Most conformational epitope (CE) prediction methods rely on the characteristics and geometrical conformations of bound antigens. However, protein complex formation may cause conformational changes on antigens and lead to various CE prediction results from an identical molecular antigen. To investigate the influence on flexible structures, this article attempts to explore the impact of structural changes on the consistency of CE prediction from two well-known prediction methods: SEPPA and DiscoTope. These two systems were adopted to evaluate the variation rate of predicted epitopes on two curated unbound/bound antigen datasets. The variation rate reflects the inconsistent level of CE prediction between unbound/bound antigens, and the experimental results have shown that conformationally deformed antigens give irregular prediction results, especially when the molecular conformations are changed significantly. It is also observed that the loop segments within an antigen play a major role in structural variation to give inconsistent CE prediction results for most available systems. We suggest that a protein surface comparison module based on deformation invariant features should be analyzed prior to CE prediction. The transition from unbound to bound structures contributes convincing prediction results since the learning procedures of known epitopes were obtained by extracting antigen structures from complex formation datasets. This evaluation system, evaluated results, and curated database are freely accessible from http://ace.cs.ntou.edu.tw/.
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