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sbliven merged 22 commits into from
Jul 22, 2015
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Extend structure alignment page with multiple alignments #5

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509057f
Adding basic alignmentcode page with MultipleStructureAlignment proposal
sbliven Jul 10, 2014
e60bfea
Explanation for AFPChain Data Model
lafita Jul 21, 2015
30a0202
Update references and section template
lafita Jul 21, 2015
f095f28
Explain MultipleAlignment object hierarchy
lafita Jul 21, 2015
ac15b5d
Include examples for the two data models
lafita Jul 21, 2015
fa0fae2
Change protein references to structure
lafita Jul 22, 2015
a45465c
Add figures for multiple GUI
lafita Jul 22, 2015
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Change multiple figures
lafita Jul 22, 2015
dd2b482
Describe the GUI for multiple alignments
lafita Jul 22, 2015
3e2f422
Update structure reference in README
lafita Jul 22, 2015
3118385
Update structure references in Structure modules
lafita Jul 22, 2015
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Update first steps
lafita Jul 22, 2015
1990920
Update structure data model
lafita Jul 22, 2015
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Update caching
lafita Jul 22, 2015
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Update chemcomp.md
lafita Jul 22, 2015
77fc195
Update mmCIF explanation
lafita Jul 22, 2015
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Update SEQRES
lafita Jul 22, 2015
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Explain utility methods for MSTA manipulation
lafita Jul 22, 2015
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Description of the MultipleMC algorithm
lafita Jul 22, 2015
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Footer script compatible with python 2.6
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Merge remote-tracking branch 'origin/multiplealignment' into multiple…
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Change protein references to structure 
Since the structural alignment algorithms work for all biological structures, not only proteins, their description should be generalized.
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lafita committed Jul 22, 2015
commit fa0fae2e4d04044def6ade53a39a3af0a4716d1b
57 changes: 36 additions & 21 deletions structure/alignment.md
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Protein Structure Alignment
Structure Alignment
===========================

## What is a structure alignment?
## What is a Structure Alignment?

A **Structural alignment** attempts to establish equivalences between two or more polymer structures based on their shape and three-dimensional conformation. In contrast to simple structural superposition (see below), where at least some equivalent residues of the two structures are known, structural alignment requires no a priori knowledge of equivalent positions.
A **structural alignment** attempts to establish equivalences between two or more polymer structures based on their shape and three-dimensional conformation. In contrast to simple structural superposition (see below), where at least some equivalent residues of the two structures are known, structural alignment requires no a priori knowledge of equivalent positions.

Structural alignment is a valuable tool for the comparison of proteins with low sequence similarity, where evolutionary relationships between proteins cannot be easily detected by standard sequence alignment techniques. Structural alignment can therefore be used to imply evolutionary relationships between proteins that share very little common sequence. However, caution should be exercised when using the results as evidence for shared evolutionary ancestry, because of the possible confounding effects of convergent evolution by which multiple unrelated amino acid sequences converge on a common tertiary structure.
**Structural alignment** is a valuable tool for the comparison of proteins with low sequence similarity, where evolutionary relationships between proteins cannot be easily detected by standard sequence alignment techniques. **Structural alignment** can therefore be used to imply evolutionary relationships between proteins that share very little common sequence. However, caution should be exercised when using the results as evidence for shared evolutionary ancestry, because of the possible confounding effects of convergent evolution by which multiple unrelated amino acid sequences converge on a common tertiary structure.

For more info see the Wikipedia article on [protein structure alignment](http://en.wikipedia.org/wiki/Structural_alignment).
**Structural alignment** of other biological structures can also be made in BioJava. For example, nucleic acids can
be structurally aligned to find common structural motifs, independent of sequence simililarity. This is specially
important for RNAs, because their 3D structure arrangement is important for their function.

For more info see the Wikipedia article on [structure alignment](http://en.wikipedia.org/wiki/Structural_alignment).

## Alignment Algorithms supported by BioJava

BioJava comes with a number of algorithms for aligning structures. The following
five options are displayed by default in the graphical user interface (GUI),
although others can be accessed programmatically using the methods in
[StructureAlignmentFactory](http://www.biojava.org/docs/api/org/biojava/nbio/structure/align/StructureAlignmentFactory.html).
[StructureAlignmentFactory]
(http://www.biojava.org/docs/api/org/biojava/nbio/structure/align/StructureAlignmentFactory.html).

1. Combinatorial Extension (CE)
2. Combinatorial Extension with Circular Permutation (CE-CP)
3. FATCAT - rigid
4. FATCAT - flexible.
5. Smith-Waterman superposition

CE and FATCAT both use structural similarity to align the proteins, while
CE and FATCAT both use structural similarity to align the structures, while
Smith-Waterman performs a local sequence alignment and then displays the result
in 3D. See below for descriptions of the algorithms.

Since BioJava version 4.1.0, multiple structure alignments can be generated and visualized.
The algorithm is described in detail below. As an overview, it uses any pairwise alignment
algorithm and a reference structure to align all of the structures. Then, it runs a Monte
Carlo optimization method to determine the residue equivalencies between all the strucutures,
identifying conserved structural motifs.

## Alignment User Interface

Before going the details how to use the algorithms programmatically, let's take
Expand All @@ -39,7 +50,7 @@ This code shows the following user interface:

![Alignment GUI](img/alignment_gui.png)

You can manually select protein chains, domains, or custom files to be aligned.
You can manually select structure chains, domains, or custom files to be aligned.
Try to align 2hyn vs. 1zll. This will show the results in a graphical way, in
3D:

Expand All @@ -60,7 +71,7 @@ algorithms.
The Combinatorial Extension (CE) algorithm was originally developed by
[Shindyalov and Bourne in
1998](http://peds.oxfordjournals.org/content/11/9/739.short) [![pubmed](http://img.shields.io/badge/in-pubmed-blue.svg?style=flat)](http://www.ncbi.nlm.nih.gov/pubmed/9796821).
It works by identifying segments of the two proteins with similar local
It works by identifying segments of the two structures with similar local
structure, and then combining those to try to align the most residues possible
while keeping the overall RMSD of the superposition low.

Expand All @@ -77,15 +88,16 @@ BioJava class: [org.biojava.bio.structure.align.ce.CeMain](http://www.biojava.or
### Combinatorial Extension with Circular Permutation (CE-CP)

CE and FATCAT both assume that aligned residues occur in the same order in both
proteins (e.g. they are both *sequence-order dependent* algorithms). In proteins
structures (e.g. they are both *sequence-order dependent* algorithms). In proteins
related by a circular permutation, the N-terminal part of one protein is related
to the C-terminal part of the other, and vice versa. CE-CP allows circularly
permuted proteins to be compared. For more information on circular
permutations, see the
[Wikipedia](http://en.wikipedia.org/wiki/Circular_permutation_in_proteins) or
[Molecule of the
Month](http://www.pdb.org/pdb/101/motm.do?momID=124&evtc=Suggest&evta=Moleculeof%20the%20Month&evtl=TopBar)
articles [![pubmed](http://img.shields.io/badge/in-pubmed-blue.svg?style=flat)](http://www.ncbi.nlm.nih.gov/pubmed/22496628).
[Molecule of the Month]
(http://www.pdb.org/pdb/101/motm.do?momID=124&evtc=Suggest&evta=Moleculeof%20the%20Month&evtl=TopBar)
articles [![pubmed]
(http://img.shields.io/badge/in-pubmed-blue.svg?style=flat)](http://www.ncbi.nlm.nih.gov/pubmed/22496628).


For proteins without a circular permutation, CE-CP results look very similar to
Expand All @@ -97,23 +109,24 @@ proteins will be shown in different colors:

CE-CP was developed by Spencer E. Bliven, Philip E. Bourne, and Andreas Prlić.

BioJava class: [org.biojava.bio.structure.align.ce.CeCPMain](http://www.biojava.org/docs/api/org/biojava/nbio/structure/align/ce/CeCPMain.html)
BioJava class: [org.biojava.nbio.structure.align.ce.CeCPMain](http://www.biojava.org/docs/api/org/biojava/nbio/structure/align/ce/CeCPMain.html)

### FATCAT - rigid

This is a Java implementation of the original FATCAT algorithm by [Yuzhen Ye
& Adam Godzik in
2003](http://bioinformatics.oxfordjournals.org/content/19/suppl_2/ii246.abstract)
[![pubmed](http://img.shields.io/badge/in-pubmed-blue.svg?style=flat)](http://www.ncbi.nlm.nih.gov/pubmed/14534198).
It performs similarly to CE for most proteins. The 'rigid' flavor uses a
It performs similarly to CE for most structures. The 'rigid' flavor uses a
rigid-body superposition and only considers alignments with matching sequence
order.

BioJava class: [org.biojava.bio.structure.align.fatcat.FatCatRigid](www.biojava.org/docs/api/org/biojava/nbio/structure/align/fatcat/FatCatRigid.html)
BioJava class: [org.biojava.nbio.structure.align.fatcat.FatCatRigid]
(www.biojava.org/docs/api/org/biojava/nbio/structure/align/fatcat/FatCatRigid.html)

### FATCAT - flexible

FATCAT-flexible introduces 'twists' between different parts of the proteins
FATCAT-flexible introduces 'twists' between different parts of the structures
which are superimposed independently. This is ideal for proteins which undergo
large conformational shifts, where a global superposition cannot capture the
underlying similarity between domains. For instance, the structures of
Expand All @@ -124,21 +137,23 @@ this is that it can lead to additional false positives in unrelated structures.
![(Left) Rigid and (Right) flexible alignments of
calmodulin](img/1cfd_1cll_fatcat.png)

BioJava class: [org.biojava.bio.structure.align.fatcat.FatCatFlexible](www.biojava.org/docs/api/org/biojava/nbio/structure/align/fatcat/FatCatFlexible.html)
BioJava class: [org.biojava.nbio.structure.align.fatcat.FatCatFlexible]
(www.biojava.org/docs/api/org/biojava/nbio/structure/align/fatcat/FatCatFlexible.html)

### Smith-Waterman

This aligns residues based on Smith and Waterman's 1981 algorithm for local
*sequence* alignment [![pubmed](http://img.shields.io/badge/in-pubmed-blue.svg?style=flat)](http://www.ncbi.nlm.nih.gov/pubmed/7265238). No structural information is included in the alignment, so
this only works for proteins with significant sequence similarity. It uses the
this only works for structures with significant sequence similarity. It uses the
Blosum65 scoring matrix.

The two structures are superimposed based on this alignment. Be aware that errors
locating gaps can lead to high RMSD in the resulting superposition due to a
small number of badly aligned residues. However, this method is faster than
the structure-based methods.

BioJava Class: [org.biojava.bio.structure.align.ce.CeCPMain](http://www.biojava.org/docs/api/org/biojava/nbio/structure/align/ce/CeCPMain.html)
BioJava Class: [org.biojava.nbio.structure.align.ce.CeCPMain]
(http://www.biojava.org/docs/api/org/biojava/nbio/structure/align/ce/CeCPMain.html)

### Other methods

Expand Down Expand Up @@ -253,7 +268,7 @@ file in various formats.

## See Also

For details about the structure alignment data models in biojava, see [Structure Alignment Data Models](alignment-data-model.md)
For details about the structure alignment data models in biojava, see [Structure Alignment Data Model](alignment-data-model.md)

## Acknowledgements

Expand Down