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Proteins comparison through probabilistic optimal structure local alignment.

Micale G, Pulvirenti A, Giugno R, Ferro A - Front Genet (2014)

Bottom Line: Only the distances between all pairs of residues in the structures are computed.To show the accuracy and the effectiveness of PROPOSAL we tested it on a few families of protein structures.We also compared PROPOSAL with two state-of-the-art tools for pairwise local alignment on a dataset of manually annotated motifs.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, University of Pisa Pisa, Italy.

ABSTRACT
Multiple local structure comparison helps to identify common structural motifs or conserved binding sites in 3D structures in distantly related proteins. Since there is no best way to compare structures and evaluate the alignment, a wide variety of techniques and different similarity scoring schemes have been proposed. Existing algorithms usually compute the best superposition of two structures or attempt to solve it as an optimization problem in a simpler setting (e.g., considering contact maps or distance matrices). Here, we present PROPOSAL (PROteins comparison through Probabilistic Optimal Structure local ALignment), a stochastic algorithm based on iterative sampling for multiple local alignment of protein structures. Our method can efficiently find conserved motifs across a set of protein structures. Only the distances between all pairs of residues in the structures are computed. To show the accuracy and the effectiveness of PROPOSAL we tested it on a few families of protein structures. We also compared PROPOSAL with two state-of-the-art tools for pairwise local alignment on a dataset of manually annotated motifs. PROPOSAL is available as a Java 2D standalone application or a command line program at http://ferrolab.dmi.unict.it/proposal/proposal.html.

No MeSH data available.


Related in: MedlinePlus

Running time of PROPOSAL as a function of (A) number of proteins (N); (B) w; (C) α; (D) iterRefine. Default values: N = 6, w = 15, α = 0.05, IterRefine = 10.
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Figure 10: Running time of PROPOSAL as a function of (A) number of proteins (N); (B) w; (C) α; (D) iterRefine. Default values: N = 6, w = 15, α = 0.05, IterRefine = 10.

Mentions: Next, we investigated the effects of varying PROPOSAL parameters. The default values are N = 6, w = 15, α = 0.05, and IterRefine = 10. First, we analyse how parameters influence the running time (Figure 10) by varying one parameter and leaving the rest unchanged. Figure 10A depicts the running time varying the number N of structures. Figure 10B deals with the effect of varying w from 1 to 20. Figure 10C reports the PROPOSAL behavior with α ranging from 0.01 to 0.30. Finally, in Figure 10D different values of IterRefine (from 1 to 30) are considered. As expected, when N and w grow and alpha decreases, the running time goes up. Such a trend is even more evident in the TIM Barrel family which has the highest average protein sequence length and similarity.


Proteins comparison through probabilistic optimal structure local alignment.

Micale G, Pulvirenti A, Giugno R, Ferro A - Front Genet (2014)

Running time of PROPOSAL as a function of (A) number of proteins (N); (B) w; (C) α; (D) iterRefine. Default values: N = 6, w = 15, α = 0.05, IterRefine = 10.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4151033&req=5

Figure 10: Running time of PROPOSAL as a function of (A) number of proteins (N); (B) w; (C) α; (D) iterRefine. Default values: N = 6, w = 15, α = 0.05, IterRefine = 10.
Mentions: Next, we investigated the effects of varying PROPOSAL parameters. The default values are N = 6, w = 15, α = 0.05, and IterRefine = 10. First, we analyse how parameters influence the running time (Figure 10) by varying one parameter and leaving the rest unchanged. Figure 10A depicts the running time varying the number N of structures. Figure 10B deals with the effect of varying w from 1 to 20. Figure 10C reports the PROPOSAL behavior with α ranging from 0.01 to 0.30. Finally, in Figure 10D different values of IterRefine (from 1 to 30) are considered. As expected, when N and w grow and alpha decreases, the running time goes up. Such a trend is even more evident in the TIM Barrel family which has the highest average protein sequence length and similarity.

Bottom Line: Only the distances between all pairs of residues in the structures are computed.To show the accuracy and the effectiveness of PROPOSAL we tested it on a few families of protein structures.We also compared PROPOSAL with two state-of-the-art tools for pairwise local alignment on a dataset of manually annotated motifs.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science, University of Pisa Pisa, Italy.

ABSTRACT
Multiple local structure comparison helps to identify common structural motifs or conserved binding sites in 3D structures in distantly related proteins. Since there is no best way to compare structures and evaluate the alignment, a wide variety of techniques and different similarity scoring schemes have been proposed. Existing algorithms usually compute the best superposition of two structures or attempt to solve it as an optimization problem in a simpler setting (e.g., considering contact maps or distance matrices). Here, we present PROPOSAL (PROteins comparison through Probabilistic Optimal Structure local ALignment), a stochastic algorithm based on iterative sampling for multiple local alignment of protein structures. Our method can efficiently find conserved motifs across a set of protein structures. Only the distances between all pairs of residues in the structures are computed. To show the accuracy and the effectiveness of PROPOSAL we tested it on a few families of protein structures. We also compared PROPOSAL with two state-of-the-art tools for pairwise local alignment on a dataset of manually annotated motifs. PROPOSAL is available as a Java 2D standalone application or a command line program at http://ferrolab.dmi.unict.it/proposal/proposal.html.

No MeSH data available.


Related in: MedlinePlus