31,493 research outputs found
Graph theoretic methods for the analysis of structural relationships in biological macromolecules
Subgraph isomorphism and maximum common subgraph isomorphism algorithms from graph theory provide an effective and an efficient way of identifying structural relationships between biological macromolecules. They thus provide a natural complement to the pattern matching algorithms that are used in bioinformatics to identify sequence relationships. Examples are provided of the use of graph theory to analyze proteins for which three-dimensional crystallographic or NMR structures are available, focusing on the use of the Bron-Kerbosch clique detection algorithm to identify common folding motifs and of the Ullmann subgraph isomorphism algorithm to identify patterns of amino acid residues. Our methods are also applicable to other types of biological macromolecule, such as carbohydrate and nucleic acid structures
The DNA-binding domain of the Chd1 chromatin-remodelling enzyme contains SANT and SLIDE domains
The ATP-dependent chromatin-remodelling enzyme Chd1 is a 168-kDa protein consisting of a double chromodomain, Snf2-related ATPase domain, and a C-terminal DNA-binding domain. Here, we show the DNA-binding domain is required for Saccharomyces cerevisiae Chd1 to bind and remodel nucleosomes. The crystal structure of this domain reveals the presence of structural homology to SANT and SLIDE domains previously identified in ISWI remodelling enzymes. The presence of these domains in ISWI and Chd1 chromatin-remodelling enzymes may provide a means of efficiently harnessing the action of the Snf2-related ATPase domain for the purpose of nucleosome spacing and provide an explanation for partial redundancy between these proteins. Site directed mutagenesis was used to identify residues important for DNA binding and generate a model describing the interaction of this domain with DNA. Through inclusion of Chd1 sequences in homology searches SLIDE domains were identified in CHD6–9 proteins. Point mutations to conserved amino acids within the human CHD7 SLIDE domain have been identified in patients with CHARGE syndrome
CLP-based protein fragment assembly
The paper investigates a novel approach, based on Constraint Logic
Programming (CLP), to predict the 3D conformation of a protein via fragments
assembly. The fragments are extracted by a preprocessor-also developed for this
work- from a database of known protein structures that clusters and classifies
the fragments according to similarity and frequency. The problem of assembling
fragments into a complete conformation is mapped to a constraint solving
problem and solved using CLP. The constraint-based model uses a medium
discretization degree Ca-side chain centroid protein model that offers
efficiency and a good approximation for space filling. The approach adapts
existing energy models to the protein representation used and applies a large
neighboring search strategy. The results shows the feasibility and efficiency
of the method. The declarative nature of the solution allows to include future
extensions, e.g., different size fragments for better accuracy.Comment: special issue dedicated to ICLP 201
Comprehensive structural classification of ligand binding motifs in proteins
Comprehensive knowledge of protein-ligand interactions should provide a
useful basis for annotating protein functions, studying protein evolution,
engineering enzymatic activity, and designing drugs. To investigate the
diversity and universality of ligand binding sites in protein structures, we
conducted the all-against-all atomic-level structural comparison of over
180,000 ligand binding sites found in all the known structures in the Protein
Data Bank by using a recently developed database search and alignment
algorithm. By applying a hybrid top-down-bottom-up clustering analysis to the
comparison results, we determined approximately 3000 well-defined structural
motifs of ligand binding sites. Apart from a handful of exceptions, most
structural motifs were found to be confined within single families or
superfamilies, and to be associated with particular ligands. Furthermore, we
analyzed the components of the similarity network and enumerated more than 4000
pairs of ligand binding sites that were shared across different protein folds.Comment: 13 pages, 8 figure
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