Abstract
BackgroundThe conventional superposition methods use an ordinary least squares (LS) fit for structural comparison of two different conformations of the same protein. The main problem of the LS fit that it is sensitive to outliers, i.e. large displacements of the original structures superimposed.ResultsTo overcome this problem, we present a new algorithm to overlap two protein conformations by their atomic coordinates using a robust statistics technique: least median of squares (LMS). In order to effectively approximate the LMS optimization, the forward search technique is utilized. Our algorithm can automatically detect and superimpose the rigid core regions of two conformations with small or large displacements. In contrast, most existing superposition techniques strongly depend on the initial LS estimating for the entire atom sets of proteins. They may fail on structural superposition of two conformations with large displacements. The presented LMS fit can be considered as an alternative and complementary tool for structural superposition.ConclusionThe proposed algorithm is robust and does not require any prior knowledge of the flexible regions. Furthermore, we show that the LMS fit can be extended to multiple level superposition between two conformations with several rigid domains. Our fit tool has produced successful superpositions when applied to proteins for which two conformations are known. The binary executable program for Windows platform, tested examples, and database are available from .
Highlights
The conventional superposition methods use an ordinary least squares (LS) fit for structural comparison of two different conformations of the same protein
We have presented a novel technique of structural superposition for flexible proteins
The method is based on least median of squares (LMS) for guiding the classical root mean square deviation (RMSD) fit
Summary
The conventional superposition methods use an ordinary least squares (LS) fit for structural comparison of two different conformations of the same protein. Protein flexibility is of great interest due to its essential role in various biological processes. The flexibility of dynamic regions allows a protein to assume multiple conformational states. Protein conformational changes play a critical role in biological functions such as ligand-protein and protein-protein interactions [1,2,3,4,5]. The rigid regions of the protein with highly structural stability will remain relatively unchanged between the multiple conformations in spite of any movement of the flexible regions [2,3,4]. In order to understand this kind of biological process, it is the first step to find out which regions keep the same and which change between two or multiple conformations. Structural superposition, defined as laying one molecule over the other by appropriate rotation and translation, is a common way to achieve that goal [2,6,7,8]
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