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Structure- and sequence-based function prediction for non-homologous proteins

  • Published:
Journal of Structural and Functional Genomics

Abstract

The structural genomics projects have been accumulating an increasing number of protein structures, many of which remain functionally unknown. In parallel effort to experimental methods, computational methods are expected to make a significant contribution for functional elucidation of such proteins. However, conventional computational methods that transfer functions from homologous proteins do not help much for these uncharacterized protein structures because they do not have apparent structural or sequence similarity with the known proteins. Here, we briefly review two avenues of computational function prediction methods, i.e. structure-based methods and sequence-based methods. The focus is on our recent developments of local structure-based and sequence-based methods, which can effectively extract function information from distantly related proteins. Two structure-based methods, Pocket-Surfer and Patch-Surfer, identify similar known ligand binding sites for pocket regions in a query protein without using global protein fold similarity information. Two sequence-based methods, protein function prediction and extended similarity group, make use of weakly similar sequences that are conventionally discarded in homology based function annotation. Combined together with experimental methods we hope that computational methods will make leading contribution in functional elucidation of the protein structures.

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Abbreviations

PDB:

Protein Data Bank

3DZD:

3 Dimensional Zernike descriptor

ATP:

Adenosine triphosphate

HEM:

Heme

NAD:

Nicotinamide adenine dinucleotide

FAD:

Flavin adenine dinucleotide

BTN:

Biotin

F6P:

Fructose 6-phosphate

GUN:

Guanine

PLM:

Palmitic acid

RTL:

Retinol

AUC:

Area under the curve

ROC:

Receiver operator characteristic

EF:

Enrichment factor

GO:

Gene ontology

PFP:

Protein function prediction

ESG:

Extended similarity group

AFP-SIG:

Automatic Function Prediction Special Interest Group

ISMB:

Intelligent System in Molecular Biology

CASP:

Critical Assessment of Techniques for Protein Structure Prediction

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Acknowledgments

This work is supported in part by the National Institute of General Medical Sciences of the National Institutes of Health (R01GM075004, R01GM097528), the National Science Foundation (DMS0800568, EF0850009, IIS0915801) and Showalter Trust. MC is supported by Bilsland Dissertation Fellowship from College of Science, Purdue University.

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Authors and Affiliations

  1. Department of Computer Science, Purdue University, West Lafayette, IN, 47907, USA

    Lee Sael, Meghana Chitale & Daisuke Kihara

  2. Department of Biological Sciences, Purdue University, West Lafayette, IN, 47907, USA

    Lee Sael & Daisuke Kihara

  3. Markey Center for Structural Biology, Purdue University, West Lafayette, IN, 47907, USA

    Lee Sael & Daisuke Kihara

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  1. Lee Sael
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  2. Meghana Chitale
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Correspondence to Daisuke Kihara.

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Lee Sael and Meghana Chitale contributed equally to this article.

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Sael, L., Chitale, M. & Kihara, D. Structure- and sequence-based function prediction for non-homologous proteins. J Struct Funct Genomics 13, 111–123 (2012). https://doi.org/10.1007/s10969-012-9126-6

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