The importance of short structural motifs in protein structure analysis

Unger, Ron; Sussman, Joel L.

doi:10.1007/bf02337561

Cited by 49 publications

(37 citation statements)

References 40 publications

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“…Because the HSSP database includes at least one sequence of known three-dimensional structure per multiple sequence alignment, the structure (13).…”

Section: Resultsmentioning

confidence: 99%

Global properties of the mapping between local amino acid sequence and local structure in proteins.

Han

Baker

1996

Proc. Natl. Acad. Sci. U.S.A.

114

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Local protein structure prediction efforts have consistently failed to exceed -70% accuracy. We characterize the degeneracy of the mapping from local sequence to local structure responsible for this failure by investigating the extent to which similar sequence segments found in different proteins adopt similar three-dimensional structures. Sequence segments 3-15 residues in length from 154 different protein families are partitioned into neighborhoods containing segments with similar sequences using cluster analysis. The consistency of the sequence-to-structure mapping is assessed by comparing the local structures adopted by sequence segments in the same neighborhood in proteins of known structure. In the 154 families, 45% and 28% of the positions occur in neighborhoods in which one and two local structures predominate, respectively. The sequence patterns that characterize the neighborhoods in the first class probably include virtually all of the short sequence motifs in proteins that consistently occur in a particular local structure. These patterns, many of which occur in transitions between secondary structural elements, are an interesting combination of previously studied and novel motifs. The identification of sequence patterns that consistently occur in one or a small number of local structures in proteins should contribute to the prediction of protein structure from sequence.Most studies of local sequence-structure relationships have involved the tabulation of statistics on sequences that occur in structural motifs of interest (1-4) (Fig. 1A). Our approach (Fig. 1B) is essentially the inverse. Instead of investigating the sequence patterns found in predefined local structural environments, we first identify recurring sequence patterns and then investigate their structural correlates.It is well established that the local sequence-to-structure mapping is not one to one over all of sequence space: identical pentapeptide sequences exist in completely different tertiary structures in proteins (5). Furthermore, local structure prediction efforts consistently fail to exceed -70% accuracy (6), suggesting that the mapping from local sequence to structure is likely to be degenerate for a significant fraction of sequence space. In this paper we characterize the degeneracy of the mapping by determining the number of sequence segments in neighborhoods (regions of sequence space) in which the sequence-to-structure mapping is one to one, one to two, and one to three (Fig. 1B). In previous work (9), we utilized a measure of the distance between sequence profiles generated from multiple sequence alignments to identify sequence patterns that transcend protein family boundaries. A similar distance measure is used in this paper, and the term "segment" below refers to a segment of a profile generated from a multiple sequence alignment.The earlier work focused on the identification and characterization of recurring sequence patterns; the focus of the current paper is on the structural correlates of these patterns. Metho...

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“…Because the HSSP database includes at least one sequence of known three-dimensional structure per multiple sequence alignment, the structure (13).…”

Section: Resultsmentioning

confidence: 99%

Global properties of the mapping between local amino acid sequence and local structure in proteins.

Han

Baker

1996

Proc. Natl. Acad. Sci. U.S.A.

114

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“…Most attempts to identify such relationships have proceeded by identifying a common structural motif, then characterizing the frequencies of occurrence of each amino acid at each position in the motif (Aurora et al, 1994;Chan et al, 1993;E®mov, 1993;Hutchinson & Thornton, 1994;Jime Ânez et al, 1994;Unger & Sussman, 1993;Zhu & Blundell, 1996). In particular, sequence patterns for tight turns (Hutchinson & Thornton, 1994;Yang et al, 1996) and helix caps (Aurora et al, 1994;Donnelly et al, 1994;elMasry & Fersht, 1994;Jime Ânez et al, 1994; have been described.…”

Section: Introductionmentioning

confidence: 99%

“…The procedure may be viewed as a combination of previous sequence-based and structurebased clustering approaches (Han & Baker, 1995Oliva et al, 1997;Rooman et al, 1900;Unger and Sussman, 1993). Starting with sequence-based clusters, the most frequently occurring structure in each cluster is chosen as the structural``paradigm''.…”

Section: Introductionmentioning

confidence: 99%

Prediction of local structure in proteins using a library of sequence-structure motifs

Bystroff

Baker

1998

Journal of Molecular Biology

310

267

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We describe a new method for local protein structure prediction based on a library of short sequence pattern that correlate strongly with protein three-dimensional structural elements. The library was generated using an automated method for ®nding correlations between protein sequence and local structure, and contains most previously described local sequence-structure correlations as well as new relationships, including a diverging type-II b-turn, a frayed helix, and a proline-terminated helix. The query sequence is scanned for segments 7 to 19 residues in length that strongly match one of the 82 patterns in the library. Matching segments are assigned the three-dimensional structure characteristic of the corresponding sequence pattern, and backbone torsion angles for the entire query sequence are then predicted by piecing together mutually compatible segment predictions. In predictions of local structure in a test set of 55 proteins, about 50% of all residues, and 76% of residues covered by high-con®dence predictions, were found in eight-residue segments within 1.4 A Ê of their true structures. The predictions are complementary to traditional secondary structure predictions because they are considerably more speci®c in turn regions, and may contribute to ab initio tertiary structure prediction and fold recognition.

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“…The structural alphabet represents advantageous local structures and has been used to 1) compare/analyze 3D structures [14]- [16], 2) predict protein 3D structures from amino acid sequences [6], [9], 3) reconstruct protein backbones [11], and 4) model loops [17]. In addition, given that local structures are generally more evolutionary conserved than amino acid sequences, a series of research has been developed to explore protein structures [18].…”

Section: Introductionmentioning

confidence: 99%

A Complex Network Approach for the Analysis of Protein Units Similarity Using Structural Alphabet

Tung¹,

Nacher²

2013

IJBBB

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Abstract-In this paper we present a network approach based on the recent developed 3D-BLAST method of rapid protein structure search. We defined new local segments that represent structural feature of proteins named units of structural alphabet (USA). Each USA is composed of two protein secondary structures, and one loop located between these two secondary structures. We performed all-against-all structural comparison of USA and recognized the USA-based similarity network. The analytical result shows that the network with a power degree distribution is called scale free. These results not only suggest the existence of organizing principles in the local protein structure but also allow us to identify potential key fragments that could be useful for future new drug development and design.Index Terms-Local structure similarity network, network biology, protein modularity. I. INTRODUCTIONIn the past few decades, genomics (DNA sequences), structural genomics (protein structures), and proteomics (protein expression and interactions) have rapidly enhanced knowledge on biological functions and systems. With structural models developed using genome-wide investigative strategies [1]-[3], the number of protein structures in the Protein Data Bank (PDB) has rapidly increased. By Dec. 25, 2012, there were already more than 87,090 known protein structures [4]. The increasing number of known protein structures with unknown/unassigned functions emphasizes the demand for effective bioinformatics methods for annotating the structural homology or evolutionary family of proteins and inferring their cellular functions.The comparison and analysis of the relationship between new protein structures with unclear functions and well-known structures seeks to bridge the protein structure-function research gap. Given a query protein structure, we may search through the database and report similar protein structures. However, unlike one-dimensional sequence comparison, structural alignment for determining similarities is much more complex and computationally expensive. Some methods can be used for efficient pair-wise Manuscript received January 15, 2013; revised March 15, 2013. This work was supported in part by the National Science Council (NSC), Taiwan, under Contract of NSC 101-2311-B-216-001 and 101-2221-E-216-041.Chi-Hua Tung is with the Department of Bioinformatics, Chung-Hua University, Hsinchu 300, Taiwan (e-mail: chihua.tung@chu.edu.tw).Jose C. Nacher is with Department of Information Science, Faculty of Science, Toho University, Miyama 2-2-1, Funabashi, Chiba 274-8510, Japan (e-mail: nacher@is.sci.toho-u.ac.jp). structural comparison [5], but these methods entail an exhaustive search to compare the query structure against all protein structures in the database.To bridge the current protein structure-function research gap and address anterior questions, many approaches have been proposed for encoding 3D local structural fragments based on Cartesian coordinates into a one-dimensional representation using several letters called the str...

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The importance of short structural motifs in protein structure analysis

Cited by 49 publications

References 40 publications

Global properties of the mapping between local amino acid sequence and local structure in proteins.

Global properties of the mapping between local amino acid sequence and local structure in proteins.

Prediction of local structure in proteins using a library of sequence-structure motifs

A Complex Network Approach for the Analysis of Protein Units Similarity Using Structural Alphabet

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