Abstract
BackgroundProteins that share a high sequence homology while exhibiting drastically different 3D structures are investigated in this study. Recently, artificial proteins related to the sequences of the GA and IgG binding GB domains of human serum albumin have been designed. These artificial proteins, referred to as GA and GB, share 98% amino acid sequence identity but exhibit different 3D structures, namely, a 3α bundle versus a 4β + α structure. Discriminating between their 3D structures based on their amino acid sequences is a very difficult problem. In the present work, in addition to using bioinformatics techniques, an analysis based on inter-residue average distance statistics is used to address this problem.ResultsIt was hard to distinguish which structure a given sequence would take only with the results of ordinary analyses like BLAST and conservation analyses. However, in addition to these analyses, with the analysis based on the inter-residue average distance statistics and our sequence tendency analysis, we could infer which part would play an important role in its structural formation.ConclusionsThe results suggest possible determinants of the different 3D structures for sequences with high sequence identity. The possibility of discriminating between the 3D structures based on the given sequences is also discussed.Electronic supplementary materialThe online version of this article (doi:10.1186/1756-0500-7-654) contains supplementary material, which is available to authorized users.
Highlights
Proteins that share a high sequence homology while exhibiting drastically different 3D structures are investigated in this study
In molecular bioinformatics, elucidating how a protein folds into its native structure is a significant unsolved problem that is related to the modelling and design of new protein 3D structures
We examine whether the inter-residue average distance statistics can be used to extract new information on 3D structures from these sequences in addition to the information gained from the standard sequence analysis techniques
Summary
Proteins that share a high sequence homology while exhibiting drastically different 3D structures are investigated in this study. Artificial proteins related to the sequences of the GA and IgG binding GB domains of human serum albumin have been designed These artificial proteins, referred to as GA and GB, share 98% amino acid sequence identity but exhibit different 3D structures, namely, a 3α bundle versus a 4β + α structure. Discriminating between their 3D structures based on their amino acid sequences is a very difficult problem. In molecular bioinformatics, elucidating how a protein folds into its native structure is a significant unsolved problem that is related to the modelling and design of new protein 3D structures To address this problem, we have to understand the relationship between the amino acid sequence and the 3D structure of a protein. Discriminating between two alternative structures with a very high sequence identity on the basis of energetics simulations is considered difficult [5]
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