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Structural re-alignment in an immunogenic surface region of ricin A chain.

Zemla AT, Ecale Zhou CL - Bioinform Biol Insights (2008)

Bottom Line: We compared structure alignments generated by several protein structure comparison programs to determine whether existing methods would satisfactorily align residues at a highly conserved position within an immunogenic loop in ribosome inactivating proteins (RIPs).Using default settings, structure alignments generated by several programs (CE, DaliLite, FATCAT, LGA, MAMMOTH, MATRAS, SHEBA, SSM) failed to align the respective conserved residues, although LGA reported correct residue-residue (R-R) correspondences when the beta-carbon (Cb) position was used as the point of reference in the alignment calculations.Results suggest that approaches to structure alignment employing alternate point representations corresponding to side chain position may yield structure alignments that are more consistent with observed conservation of functional surface residues than do standard alignment programs, which apply uniform criteria for alignment (i.e. alpha carbon (Ca) as point of reference) along the entirety of the peptide chain.

View Article: PubMed Central - PubMed

Affiliation: Computational Biology for Countermeasures Group, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.

ABSTRACT
We compared structure alignments generated by several protein structure comparison programs to determine whether existing methods would satisfactorily align residues at a highly conserved position within an immunogenic loop in ribosome inactivating proteins (RIPs). Using default settings, structure alignments generated by several programs (CE, DaliLite, FATCAT, LGA, MAMMOTH, MATRAS, SHEBA, SSM) failed to align the respective conserved residues, although LGA reported correct residue-residue (R-R) correspondences when the beta-carbon (Cb) position was used as the point of reference in the alignment calculations. Further tests using variable points of reference indicated that points distal from the beta carbon along a vector connecting the alpha and beta carbons yielded rigid structural alignments in which residues known to be highly conserved in RIPs were reported as corresponding residues in structural comparisons between ricin A chain, abrin-A, and other RIPs. Results suggest that approaches to structure alignment employing alternate point representations corresponding to side chain position may yield structure alignments that are more consistent with observed conservation of functional surface residues than do standard alignment programs, which apply uniform criteria for alignment (i.e. alpha carbon (Ca) as point of reference) along the entirety of the peptide chain. We present the results of tests that suggest the utility of allowing user-specified points of reference in generating alternate structural alignments, and we present a web server for automatically generating such alignments: http://as2ts.llnl.gov/AS2TS/LGA/lga_pdblist_plots.html.

No MeSH data available.


Related in: MedlinePlus

Graphical representation of structural deviations between residues of 1br6_A (ricin) and 1abr_A (abrin) aligned using LGA with varying points of representation. Each bar represents a different superposition, using a distinct point of representation. Shown are structural deviations for the alignment shown in the first and last sequence fragments of Fig. 1A. Colored bars indicate R-R distance ranges: residues superimposed below 2.0 Ǻ are in green, below 4.0Ǻ are in yellow, below 6.0Ǻ are in orange, below 8.0Ǻ are in brown, and at or above 8.0Ǻ are in red. Lower-case letter indicates residue that was not assigned correspondence, due to distance cutoffs being exceeded.
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f3-bbi-2008-005: Graphical representation of structural deviations between residues of 1br6_A (ricin) and 1abr_A (abrin) aligned using LGA with varying points of representation. Each bar represents a different superposition, using a distinct point of representation. Shown are structural deviations for the alignment shown in the first and last sequence fragments of Fig. 1A. Colored bars indicate R-R distance ranges: residues superimposed below 2.0 Ǻ are in green, below 4.0Ǻ are in yellow, below 6.0Ǻ are in orange, below 8.0Ǻ are in brown, and at or above 8.0Ǻ are in red. Lower-case letter indicates residue that was not assigned correspondence, due to distance cutoffs being exceeded.

Mentions: LGA was used in sequence-dependent mode to superimpose ricin A chain (1br6_A) and abrin-A (1abr_A) (Zemla, 2003). Sequence-dependent mode imposes a fixed R-R correspondence when calculating an optimal alignment. A series of superpositions was generated; each superposition was calculated using a different input “-cb” parameter value, which specifies a point of representation along a vector in the direction from the alpha carbon to the beta carbon, with the point of origin being 0.0 at the alpha carbon (-cb:0.0). Possible points of representation range from below the alpha carbon (negative values) to beyond the beta carbon (values >1.0). Points of representation were selected spanning from −1.0 to 3.0 in increments of 0.2, where 1.0 unit corresponds to Cb-Ca distance between the alpha carbon and beta carbon atoms (Fig. 3).


Structural re-alignment in an immunogenic surface region of ricin A chain.

Zemla AT, Ecale Zhou CL - Bioinform Biol Insights (2008)

Graphical representation of structural deviations between residues of 1br6_A (ricin) and 1abr_A (abrin) aligned using LGA with varying points of representation. Each bar represents a different superposition, using a distinct point of representation. Shown are structural deviations for the alignment shown in the first and last sequence fragments of Fig. 1A. Colored bars indicate R-R distance ranges: residues superimposed below 2.0 Ǻ are in green, below 4.0Ǻ are in yellow, below 6.0Ǻ are in orange, below 8.0Ǻ are in brown, and at or above 8.0Ǻ are in red. Lower-case letter indicates residue that was not assigned correspondence, due to distance cutoffs being exceeded.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC2735970&req=5

f3-bbi-2008-005: Graphical representation of structural deviations between residues of 1br6_A (ricin) and 1abr_A (abrin) aligned using LGA with varying points of representation. Each bar represents a different superposition, using a distinct point of representation. Shown are structural deviations for the alignment shown in the first and last sequence fragments of Fig. 1A. Colored bars indicate R-R distance ranges: residues superimposed below 2.0 Ǻ are in green, below 4.0Ǻ are in yellow, below 6.0Ǻ are in orange, below 8.0Ǻ are in brown, and at or above 8.0Ǻ are in red. Lower-case letter indicates residue that was not assigned correspondence, due to distance cutoffs being exceeded.
Mentions: LGA was used in sequence-dependent mode to superimpose ricin A chain (1br6_A) and abrin-A (1abr_A) (Zemla, 2003). Sequence-dependent mode imposes a fixed R-R correspondence when calculating an optimal alignment. A series of superpositions was generated; each superposition was calculated using a different input “-cb” parameter value, which specifies a point of representation along a vector in the direction from the alpha carbon to the beta carbon, with the point of origin being 0.0 at the alpha carbon (-cb:0.0). Possible points of representation range from below the alpha carbon (negative values) to beyond the beta carbon (values >1.0). Points of representation were selected spanning from −1.0 to 3.0 in increments of 0.2, where 1.0 unit corresponds to Cb-Ca distance between the alpha carbon and beta carbon atoms (Fig. 3).

Bottom Line: We compared structure alignments generated by several protein structure comparison programs to determine whether existing methods would satisfactorily align residues at a highly conserved position within an immunogenic loop in ribosome inactivating proteins (RIPs).Using default settings, structure alignments generated by several programs (CE, DaliLite, FATCAT, LGA, MAMMOTH, MATRAS, SHEBA, SSM) failed to align the respective conserved residues, although LGA reported correct residue-residue (R-R) correspondences when the beta-carbon (Cb) position was used as the point of reference in the alignment calculations.Results suggest that approaches to structure alignment employing alternate point representations corresponding to side chain position may yield structure alignments that are more consistent with observed conservation of functional surface residues than do standard alignment programs, which apply uniform criteria for alignment (i.e. alpha carbon (Ca) as point of reference) along the entirety of the peptide chain.

View Article: PubMed Central - PubMed

Affiliation: Computational Biology for Countermeasures Group, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA.

ABSTRACT
We compared structure alignments generated by several protein structure comparison programs to determine whether existing methods would satisfactorily align residues at a highly conserved position within an immunogenic loop in ribosome inactivating proteins (RIPs). Using default settings, structure alignments generated by several programs (CE, DaliLite, FATCAT, LGA, MAMMOTH, MATRAS, SHEBA, SSM) failed to align the respective conserved residues, although LGA reported correct residue-residue (R-R) correspondences when the beta-carbon (Cb) position was used as the point of reference in the alignment calculations. Further tests using variable points of reference indicated that points distal from the beta carbon along a vector connecting the alpha and beta carbons yielded rigid structural alignments in which residues known to be highly conserved in RIPs were reported as corresponding residues in structural comparisons between ricin A chain, abrin-A, and other RIPs. Results suggest that approaches to structure alignment employing alternate point representations corresponding to side chain position may yield structure alignments that are more consistent with observed conservation of functional surface residues than do standard alignment programs, which apply uniform criteria for alignment (i.e. alpha carbon (Ca) as point of reference) along the entirety of the peptide chain. We present the results of tests that suggest the utility of allowing user-specified points of reference in generating alternate structural alignments, and we present a web server for automatically generating such alignments: http://as2ts.llnl.gov/AS2TS/LGA/lga_pdblist_plots.html.

No MeSH data available.


Related in: MedlinePlus