Transcript Structural_compariso..
By: Z. S. Rezaei
Structural comparison
Structural alignment spectrum of structural alignment methods The properties of output Types of comparison Algorithmic complexity Representation of structures Distance matrix Methods Alignment of large RNA molecules The classes of scoring
Structural alignment
homology between two or more polymer (2) a window into the distant past of protein evolution(1) identification homologous(1) imply evolutionary relationships between proteins that share very little common sequence(2) prediction of the functions and the family of the query protein(2)
rely on information about conformations.( from X-ray crystallography or NMR spectroscopy or structure prediction methods) for evaluating prediction methods
spectrum of structural alignment methods(1)
The properties of out put
a superposition of the atomic coordinate sets and a minimal RMSD.
existence of multiple protein domains complicates the Structural alignment a set of superposed three-dimensional coordinates for each input structure(2)
the
root mean square
(
RMS
) (3)
A geometrical system Determination uniquely a spatial element
Coordinate system
Spatial coordinate Planar coordinate
Types of comparisons
Structural superposition used to compare multiple conformations of the same protein uses a simple least-squares fitting algorithm(2) Alignment Algorithms based on multidimensional rotations and modified quaternions (2)
a number system In mathematics a quaternion as the quotient of two directed lines in a three-dimensional represented as the sum of a scalar and a vector (6) Definition of quaternion
Algorithmic complexity
Optimal solution
Approximate solution(2)
Optimal solution
The optimal "threading" shown to be NP-complete Strictly speaking, an optimal solution is only known for certain protein structure similarity measures the algorithm for optimal solution is not practical (2)
Approximate solution
Approximate polynomial-time algorithms for structural alignment theoretically classify the approximate protein structure alignment(2)
Representation of structures Protein structurrepresented in some coordinate-independent space by constructing series of matrices (2)
distance matrix
a two-dimensional matrix distances between some subset of the atoms (such as the alpha carbons) Reducing the protein to a coarse metric such as secondary structure elements (SSEs)(2)
Methods(2)
DALI Combinatorial extension(CE) GANGSTA+ MAMMOTH ProBiS RAPIDO SABERTOOTH SSAP Spalign TOPOFIT SSM
DALI
distance alignment matrix method breaks the input structures into hexapeptide fragments and calculates a distance matrix Distance matrix has two diagonals conducted via a series of overlapping submatrices of size 6x6 Submatrix matches are reassembled into a final alignment
DALI
The original version used a Monte Carlo simulation The DALI method has also been used to construct a database known as FSSP (Fold classification based on Structure-Structure alignment of Proteins, or Families of Structurally Similar Proteins) There is an searchable database based on DALI as well as a downloadable program and web search based on a standalone version known as DaliLite.
Montecarlo method
a class of computational algorithms relies on repeated random sampling to compute their results especially useful for simulating systems with many coupled degrees of freedom, such as fluids, disordered materials, strongly coupled solids, and cellular structures (4)
http://ehkinda.biocenter.helsinki.fi/dali_server/
http://ebi.ac.uk/Tools/structure/dalilite
http://ebi.ac.uk/Tools/structure/dalilite
http://ebi.ac.uk/Tools/structure/dalilite
http://ebi.ac.uk/Tools/structure/dalilite
Combinatorial extension(CE)
is similar to DALI uses AFPs to define a similarity matrix A number of similarity metrics are possible
Combinatorial extension(CE)
initial AFP pair that nucleates the alignment proceed with the next AFP The RCSB PDB has recently released an updated version of CE and FATCAT as part of the RCSB PDB Protein Comparison Tool provides a new variation of CE that can detect circular permutations in protein structures
Circular permutations
A
circular permutation
shape(7) is a relationship between proteins whereby the proteins have a changed order of amino acids in their peptide sequence. The result is a protein structure with different connectivity, but overall similar three dimensional (3D)
GANGSTA+
A combinatorial algorithm for non-sequential structural alignment of proteins searching for similarity in databases (http://agknapp.chemie.fu-berlin.de/gplus/) evaluates based on contact maps and secondry structure
MAMMOTH
MA
tching
M
olecular
M
odels
O
btained from
Th
eory For comparing models coming from structure prediction decompose the protein structure into heptapeptides The similarity score between two heptapeptides is calculated using a unit-vector RMS (URMS) method These scores are stored in a similarity matrix Derived from the likelihood of obtaining a given structural alignment by chance
MAMMOTH-mult
extension of the MAMMOTH algorithm is very fast produces consistent and high quality structural alignments produces structurally implied sequence alignments that can be further used for multiple-template homology modeling
ProBiS
Pro
tein
Bi
nding
S
ites.
ProBiS
detects structurally similar sites on protein surfaces compares the query protein to members of a database of protein 3D structures Using an efficient maximum clique algorithm Structural similarity scores are calculated for the query protein’s surface residues, and are expressed as different colors used successfully for the detection of protein – protein, protein –small ligand and protein–DNA binding sites
RAPIDO
R
apid
A
lignment of
P
roteins
I
n terms of
Do
mains a web server for the 3D alignment of crystal using an approach based on difference distance matrices The Matching Fragment Pairs (MFPs) are then represented as nodes in a graph nodes in graph are chained together to form an alignment by means of an algorithm for the identification of the longest path on a DAG (Directed Acyclic Graph). The final step: improve the quality of the alignment
SABERTOOTH
structural profiles to perform structural alignments has favourable scaling of computation time with chain length SABERTOOTH can be used online at http://www.fkp.tu-darmstadt.de/sabertooth/
SSAP
Sequential Structure Alignment Program uses double dynamic programming constructs its vectors from the beta carbons for all residues except glycine A series of matrices are constructed Dynamic programming applied to each resulting matrix matrices are then summed into a "summary" matrix to Final dynamic programming is applied again to determine the overall structural alignment
SSAP
originally produced only pairwise alignments but has since been extended to multiple alignments as well applied in an all-to-all fashion to produce a hierarchical fold classification scheme known as CATH (Class, Architecture, Topology, Homology) construct the CATH Protein Structure Classification database
SPalign
Based on a new size-independent score called SPscore for The source code for SPalign and the server are available at http://sparks.informatics.iupui.edu/yueyang/ server/SPalign/
TOPOFIT
Based on Delaunay tessellation (DT) identifies a feature point on the RMSD/Ne curve topomax point to detect conformational changes, topological differences in variable parts
SSM
Secondary Structure Matching (SSM), or PDBeFold at the Protein Data Bank in Europe uses graph matching followed by c alpha alignment to compute alignments
Recent Developments
Tmalign uses a novel method for weighting its distance matrix correct for effects arising from alignment lengths
RNA structural alignment
large RNA molecules also form characteristic tertiary structures A recent method for pairwise structural alignment of RNA sequences implemented in the program FOLDALIGN In low sequence identity cases
(1)
References
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Hitomi Hasegawa and Liisa Holm: Advances and pitfalls of protein structural alignment, Current Opinion in Structural Biology 2009, 19:341 –348 en.wikipedia.org/wiki/structural_alignment software Cartwright, Kenneth V (Fall 2007). "Determining the Effective or RMS Voltage of Various Waveforms without Calculus".
Technology Interface
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(1): 20 pages Anderson, H.L. (1986). "Metropolis, Monte Carlo and the MANIAC". Los Alamos Science 14 : 96 –108 Weisstein, Eric W., "Coordinate System" from MathWorld Boris Abramovich Rozenfelʹd (1988).
The history of non-euclidean geometry: evolution of the concept of a geometric space
. Springer. p. 385 Cunningham, B. A.; Hemperly, J. J.; Hopp, T. P.; Edelman, G. M. (1979). "Favin versus concanavalin A: Circularly permuted amino acid sequences".
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