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Accuracy of functional surfaces on comparatively modeled protein structures

  • Published:
Journal of Structural and Functional Genomics

Abstract

Identification and characterization of protein functional surfaces are important for predicting protein function, understanding enzyme mechanism, and docking small compounds to proteins. As the rapid speed of accumulation of protein sequence information far exceeds that of structures, constructing accurate models of protein functional surfaces and identify their key elements become increasingly important. A promising approach is to build comparative models from sequences using known structural templates such as those obtained from structural genome projects. Here we assess how well this approach works in modeling binding surfaces. By systematically building three-dimensional comparative models of proteins using Modeller, we determine how well functional surfaces can be accurately reproduced. We use an alpha shape based pocket algorithm to compute all pockets on the modeled structures, and conduct a large-scale computation of similarity measurements (pocket RMSD and fraction of functional atoms captured) for 26,590 modeled enzyme protein structures. Overall, we find that when the sequence fragment of the binding surfaces has more than 45% identity to that of the template protein, the modeled surfaces have on average an RMSD of 0.5 Å, and contain 48% or more of the binding surface atoms, with nearly all of the important atoms in the signatures of binding pockets captured.

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Abbreviations

PDB:

Protein data bank

EC:

Enzyme commission

CASTp:

Computed atlas of surface topography of proteins

pRMSD:

Pocket root mean square deviation

pvSOAR:

Pocket and void surface patterns of amino acid residues

SOLAR :

Signature of local active regions

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Acknowledgments

This work is supported by grants from NIH (GM079804, GM081682, GM086145, GM055876-13) and NSF (DMS-0800257).

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Authors and Affiliations

  1. Department of Bioengineering, University of Illinois at Chicago, 851 S. Morgan Street, Room 218, MC-063, Chicago, IL, 60607, USA

    Jieling Zhao, Joe Dundas, Sema Kachalo, Zheng Ouyang & Jie Liang

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  1. Jieling Zhao
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  2. Joe Dundas
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  5. Jie Liang
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Correspondence to Jieling Zhao.

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Zhao, J., Dundas, J., Kachalo, S. et al. Accuracy of functional surfaces on comparatively modeled protein structures. J Struct Funct Genomics 12, 97–107 (2011). https://doi.org/10.1007/s10969-011-9109-z

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  • DOI: https://doi.org/10.1007/s10969-011-9109-z

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