Automated Procedure for Contact-Map-Based Protein Structure Reconstruction

Automated Procedure for Contact-Map-Based Protein Structure Reconstruction Knowledge of the three-dimensional structures of ion channels allows for modeling their conductivity characteristics using biophysical models and can lead to discovering their cellular functionality. Recent studies show that quality of structure predictions can be significantly improved using protein contact site information. Therefore, a number of procedures for protein structure prediction based on their contact-map have been proposed. Their comparison is difficult due to different methodologies used for validation. In this work, a Contact Map-to-Structure pipeline (C2S_pipeline) for contact-based protein structure reconstruction is designed and validated. The C2S_pipeline can be used to reconstruct monomeric and multimeric proteins. The median RMSD of structures obtained during validation on a representative set of protein structures, equaled 5.27 Å, and the best structure was reconstructed with RMSD of 1.59 Å. The validation is followed by a detailed case study on the KcsA ion channel. Models of KcsA are reconstructed based on different portions of contact site information. Structural feature analysis of acquired KcsA models is supported by a thorough analysis of electrostatic potential distributions inside the channels. The study shows that electrostatic parameters are correlated with structural quality of models. Therefore, they can be used to discriminate between high and low quality structures. We show that 30 % of contact information is needed to obtain accurate structures of KcsA, if contacts are selected randomly. This number increases to 70 % in case of erroneous maps in which the remaining contacts or non-contacts are changed to the opposite. Furthermore, the study reveals that local reconstruction accuracy is correlated with the number of contacts in which amino acid are involved. This results in higher reconstruction accuracy in the structure core than peripheral regions. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png The Journal of Membrane Biology Springer Journals

Automated Procedure for Contact-Map-Based Protein Structure Reconstruction

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Publisher
Springer US
Copyright
Copyright © 2014 by The Author(s)
Subject
Life Sciences; Biochemistry, general; Human Physiology
ISSN
0022-2631
eISSN
1432-1424
D.O.I.
10.1007/s00232-014-9648-x
Publisher site
See Article on Publisher Site

Abstract

Knowledge of the three-dimensional structures of ion channels allows for modeling their conductivity characteristics using biophysical models and can lead to discovering their cellular functionality. Recent studies show that quality of structure predictions can be significantly improved using protein contact site information. Therefore, a number of procedures for protein structure prediction based on their contact-map have been proposed. Their comparison is difficult due to different methodologies used for validation. In this work, a Contact Map-to-Structure pipeline (C2S_pipeline) for contact-based protein structure reconstruction is designed and validated. The C2S_pipeline can be used to reconstruct monomeric and multimeric proteins. The median RMSD of structures obtained during validation on a representative set of protein structures, equaled 5.27 Å, and the best structure was reconstructed with RMSD of 1.59 Å. The validation is followed by a detailed case study on the KcsA ion channel. Models of KcsA are reconstructed based on different portions of contact site information. Structural feature analysis of acquired KcsA models is supported by a thorough analysis of electrostatic potential distributions inside the channels. The study shows that electrostatic parameters are correlated with structural quality of models. Therefore, they can be used to discriminate between high and low quality structures. We show that 30 % of contact information is needed to obtain accurate structures of KcsA, if contacts are selected randomly. This number increases to 70 % in case of erroneous maps in which the remaining contacts or non-contacts are changed to the opposite. Furthermore, the study reveals that local reconstruction accuracy is correlated with the number of contacts in which amino acid are involved. This results in higher reconstruction accuracy in the structure core than peripheral regions.

Journal

The Journal of Membrane BiologySpringer Journals

Published: Mar 29, 2014

References

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