Clustering of Protein Structural Fragments Reveals Modular Building Block Approach of Nature

Structures of peptide fragments drawn from a protein can potentially occupy a vast conformational continuum. We co-ordinatize this conformational space with the help of geometric invariants and demonstrate that the peptide conformations of the currently available protein structures are heavily biase...

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Bibliographic Details
Published in:Journal of molecular biology 2004-04, Vol.338 (3), p.611-629
Main Authors: Tendulkar, Ashish V., Joshi, Anand A., Sohoni, Milind A., Wangikar, Pramod P.
Format: Article
Language:English
Subjects:
Algorithms
Computational Biology
Evolution, Molecular
geometric invariants
loop
Peptides - chemistry
Peptides - classification
Peptides - metabolism
Phylogeny
protein structure comparison
Protein Structure, Secondary
Proteins - classification
Proteins - genetics
Proteins - metabolism
secondary structure
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Summary:Structures of peptide fragments drawn from a protein can potentially occupy a vast conformational continuum. We co-ordinatize this conformational space with the help of geometric invariants and demonstrate that the peptide conformations of the currently available protein structures are heavily biased in favor of a finite number of conformational types or structural building blocks. This is achieved by representing a peptides' backbone structure with geometric invariants and then clustering peptides based on closeness of the geometric invariants. This results in 12,903 clusters, of which 2207 are made up of peptides drawn from functionally and/or structurally related proteins. These are termed “functional” clusters and provide clues about potential functional sites. The rest of the clusters, including the largest few, are made up of peptides drawn from unrelated proteins and are termed “structural” clusters. The largest clusters are of regular secondary structures such as helices and beta strands as well as of beta hairpins. Several categories of helices and strands are discovered based on geometric differences. In addition to the known classes of loops, we discover several new classes, which will be useful in protein structure modeling. Our algorithm does not require assignment of secondary structure and, therefore, overcomes the limitations in loop classification due to ambiguity in secondary structure assignment at loop boundaries.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2004.02.047