Feedback Algorithm and Web-Server for Protein Structure Alignment

Zhao, Zhiyu; Fu, Bin; Alanis, Francisco J.; Summa, Christopher M.

doi:10.1089/cmb.2008.0075

Cited by 3 publications

(1 citation statement)

References 18 publications

(8 reference statements)

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“…These results, together with an early result which shows a related problem called threading to be NP-hard [10], have traditionally led molecular biologists to believe that the structural alignment problem is difficult in general (e.g. [11-13]), even though a PTAS exists for the problem under a broad class of distance measures [14]. Heuristic algorithms have also been proposed for many variants of structural alignment problem [15-23].…”

Section: Introductionmentioning

confidence: 99%

The difficulty of protein structure alignment under the RMSD

2013

Algorithms Mol Biol

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BackgroundProtein structure alignment is often modeled as the largest common point set (LCP) problem based on the Root Mean Square Deviation (RMSD), a measure commonly used to evaluate structural similarity. In the problem, each residue is represented by the coordinate of the Cαatom, and a structure is modeled as a sequence of 3D points. Out of two such sequences, one is to find two equal-sized subsequences of the maximum length, and a bijection between the points of the subsequences which gives an RMSD within a given threshold. The problem is considered to be difficult in terms of time complexity, but the reasons for its difficulty is not well-understood. Improving this time complexity is considered important in protein structure prediction and structural comparison, where the task of comparing very numerous structures is commonly encountered.ResultsTo study why the LCP problem is difficult, we define a natural variant of the problem, called the minimum aligned distance (MAD). In the MAD problem, the length of the subsequences to obtain is specified in the input; and instead of fulfilling a threshold, the RMSD between the points of the two subsequences is to be minimized. Our results show that the difficulty of the two problems does not lie solely in the combinatorial complexity of finding the optimal subsequences, or in the task of superimposing the structures. By placing a limit on the distance between consecutive points, and assuming that the points are specified as integral values, we show that both problems are equally difficult, in the sense that they are reducible to each other. In this case, both problems can be exactly solved in polynomial time, although the time complexity remains high.ConclusionsWe showed insights and techniques which we hope will lead to practical algorithms for the LCP problem for protein structures. The study identified two important factors in the problem’s complexity: (1) The lack of a limit in the distance between the consecutive points of a structure; (2) The arbitrariness of the precision allowed in the input values. Both issues are of little practical concern for the purpose of protein structure alignment. When these factors are removed, the LCP problem is as hard as that of minimizing the RMSD (MAD problem), and can be solved exactly in polynomial time.

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Section: Introductionmentioning

confidence: 99%

The difficulty of protein structure alignment under the RMSD

2013

Algorithms Mol Biol

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Search Similar Protein Structures With Classification, Sequence and 3d Alignments

Lu¹,

Zhao

García³

et al. 2009

J. Bioinform. Comput. Biol.

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We have developed an algorithm and web tool to search similar protein structures in the PDB (Protein Data Bank). The algorithm is a combination of a series of methods including protein classification, geometric feature extraction, sequence alignment, and 3D structure alignment. Given a protein structure, the tool can efficiently discover similar structures from hundreds of thousands of structures stored in the PDB. Our experimental results show that it is more accurate than other well-known protein search systems including PSI-BLAST, 3D-BLAST, and SSM in finding proteins that are structurally similar to the query protein, and its speed is also competitive with those systems. The algorithm has been fully implemented and is accessible online at the address http://fpsa.cs.panam.edu/, which is supported by a cluster of computers.

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Efficient protein alignment algorithm for protein search

Lu¹,

Zhao

Fu³

2010

BMC Bioinformatics

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BackgroundProteins show a great variety of 3D conformations, which can be used to infer their evolutionary relationship and to classify them into more general groups; therefore protein structure alignment algorithms are very helpful for protein biologists. However, an accurate alignment algorithm itself may be insufficient for effective discovering of structural relationships among tens of thousands of proteins. Due to the exponentially increasing amount of protein structural data, a fast and accurate structure alignment tool is necessary to access protein classification and protein similarity search; however, the complexity of current alignment algorithms are usually too high to make a fully alignment-based classification and search practical.ResultsWe have developed an efficient protein pairwise alignment algorithm and applied it to our protein search tool, which aligns a query protein structure in the pairwise manner with all protein structures in the Protein Data Bank (PDB) to output similar protein structures. The algorithm can align hundreds of pairs of protein structures in one second. Given a protein structure, the tool efficiently discovers similar structures from tens of thousands of structures stored in the PDB always in 2 minutes in a single machine and 20 seconds in our cluster of 6 machines. The algorithm has been fully implemented and is accessible online at our webserver, which is supported by a cluster of computers.ConclusionOur algorithm can work out hundreds of pairs of protein alignments in one second. Therefore, it is very suitable for protein search. Our experimental results show that it is more accurate than other well known protein search systems in finding proteins which are structurally similar at SCOP family and superfamily levels, and its speed is also competitive with those systems. In terms of the pairwise alignment performance, it is as good as some well known alignment algorithms.

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Feedback Algorithm and Web-Server for Protein Structure Alignment

Cited by 3 publications

References 18 publications

The difficulty of protein structure alignment under the RMSD

The difficulty of protein structure alignment under the RMSD

Search Similar Protein Structures With Classification, Sequence and 3d Alignments

Efficient protein alignment algorithm for protein search

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