Protein Strucure Comparison
Chapter 6,7 Orengo
Helices
• α-helix 4-turn helix, min. 4 residues310-helix 3-turn helix, min. 3 residuesπ-helix 5-turn helix, min. 5 residues
• Formed by H-Bonds between residues in the same helix
Strands and Sheets
• Formed by successive H-Bonds between residues can be far apart in sequence.
Cartoons for Secondary Structure Elements (SSE)
• Topology of Protein Structure (TOPS)– Triangular symbols represent beta strands– Circular symbols represent helices (alpha and 310)
Multiple structural alignment by CORA allows identification of consensus secondary structure and embellishments
Some families show great structural diversitySome families show great structural diversity
In 117 superfamilies relatives expanded by >2 fold or more
2DSEC algorithm2DSEC algorithm
These families represent more than half the genome sequences of known These families represent more than half the genome sequences of known foldfold
Gabrielle Reeves
Strategy
Two Approaches
Example
Intra
RMSD
Example
• Alignment– ACSL-DRTS-IRV– A-TLREKSSLIR-
• Know first 5 residues– ACSL-D– A-TLRE
But not so with structures
Dyn
amic
Pro
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ing
can
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t b
e u
sed
dir
ectl
y fo
r st
ruct
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alig
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ent
highest score alignment of entire structures
highest score alignment of first five residues
Finding optimal Root mean square deviation
Process
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Let (α 1,β1),...,(α r,β r ) Be coordinate sets of equivalenced elements
minimize the expression (Rα i + t −β i)i=1
r
∑
where R is a rotation and t is a translation
Degrees of freedom include1) Equivalenced elements2) Rotation3) Translation (usually centroid)
Example
• In two dimensions
Translation
• In two dimensions
Shift Centroids to the origin
Example HW 9.2
• In two dimensions• Rotation Matrix
-0.70721358 0.707213580.70721358 0.70721358
The matrix in the book is just an angular rotation
The first step
• Transpose centroids to the origin
• Foreach angular displacement in x– Foreach angular displacement in y
• Foreach angular displacement in x– Calculate RMSD– If this RMSD is less than current minimum, save it
But, how did we get the equivalenced elements?
• First seed the problem with an initial equivalence E0
• Then find the Transformation that results in a minimum RMSD
• Use this Transformation to find a better equivalence
Alternating Superposition and Alignment
Example
The best rotation and translation is then found and a newalignment is generated
Structural Classification of Proteins (SCOP)
SCOP describes protein structures using a hierarchical classification scheme:
ClassesFoldsSuperfamilies (likely evolutionary relationship)FamiliesDomainsIndividual PDB entries
http://scop.mrc-lmb.cam.ac.uk/scop/
Class, Architecture, Topology, andHomologous Superfamily (CATH) database
Page 293
CATH clusters proteins at four levels:
C Class (, , & folds)A Architecture (shape of domain, e.g. jelly roll)T Topology (fold families; not necessarily homologous)H Homologous superfamily
http://www.biochem.ucl.ac.uk/basm/cath_new
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