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Identification of family-specific residue packing motifs and their use for structure-based protein function prediction: I. Method development

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Abstract

Protein function prediction is one of the central problems in computational biology. We present a novel automated protein structure-based function prediction method using libraries of local residue packing patterns that are common to most proteins in a known functional family. Critical to this approach is the representation of a protein structure as a graph where residue vertices (residue name used as a vertex label) are connected by geometrical proximity edges. The approach employs two steps. First, it uses a fast subgraph mining algorithm to find all occurrences of family-specific labeled subgraphs for all well characterized protein structural and functional families. Second, it queries a new structure for occurrences of a set of motifs characteristic of a known family, using a graph index to speed up Ullman’s subgraph isomorphism algorithm. The confidence of function inference from structure depends on the number of family-specific motifs found in the query structure compared with their distribution in a large non-redundant database of proteins. This method can assign a new structure to a specific functional family in cases where sequence alignments, sequence patterns, structural superposition and active site templates fail to provide accurate annotation.

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Notes

  1. Enzymes database http://www.ebi.ac.uk/thornton-srv/databases/enzymes, and flat file downloaded from http://www.ebi.ac.uk/thornton-srv/databases/pdbsum/data/seqdata.dat.

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Acknowledgments

These studies were supported by NIH grant GM068665 and NSF grant CCF-0523875.

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Authors and Affiliations

  1. GlaxoSmithKline, 1250 S. Collegeville Rd, Mail Stop UP12-210, Collegeville, PA, USA

    Deepak Bandyopadhyay

  2. Department of Electrical Engineering and Computer Science, University of Kansas, Lawrence, KS, USA

    Jun Huan

  3. Department of Computer Science, University of North Carolina, CB#3175 Sitterson Hall, Chapel Hill, NC, USA

    Jan Prins, Jack Snoeyink & Wei Wang

  4. School of Pharmacy, University of North Carolina, CB#7360 Beard Hall, Chapel Hill, NC, USA

    Alexander Tropsha

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  1. Deepak Bandyopadhyay
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  2. Jun Huan
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  4. Jack Snoeyink
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  5. Wei Wang
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  6. Alexander Tropsha
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Correspondence to Deepak Bandyopadhyay or Alexander Tropsha.

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Bandyopadhyay, D., Huan, J., Prins, J. et al. Identification of family-specific residue packing motifs and their use for structure-based protein function prediction: I. Method development. J Comput Aided Mol Des 23, 773–784 (2009). https://doi.org/10.1007/s10822-009-9273-4

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