Related Experiment Video
Updated: Aug 10, 2026
11:42
Fabrication of Gate-tunable Graphene Devices for Scanning Tunneling Microscopy Studies with Coulomb Impurities
Published on: July 24, 2015
Prediction of viable circular permutants using a graph theoretic approach
Konrad H Paszkiewicz1, Michael J E Sternberg, Michael Lappe
1Structural Bioinformatics Group, Division of Molecular Biosciences, Imperial College London, London SW7 2AZ, UK. konrad.paszkiewicz@imperial.ac.uk
Bioinformatics (Oxford, England)
|March 18, 2006
Summary
Graph theory measures, like closeness, can predict viable protein circular permutation sites. This method outperforms solvent accessibility for designing split enzymes and understanding protein folding.
Area of Science:
- Computational Biology
- Structural Biology
- Graph Theory
Background:
- Graph-theoretic approaches are increasingly used for complex biological systems analysis.
- Application of graph theory to protein structures and residue interactions shows promise.
- Circular permutants are valuable for studying protein folding and designing split enzymes.
Purpose of the Study:
- To evaluate the graph measure 'closeness' for predicting suitable protein regions for circular permutation.
- To compare the predictive power of closeness with solvent accessibility for identifying circular permutation sites.
Main Methods:
- Utilized graph theory to analyze protein structures and residue interaction networks.
- Applied the 'closeness' centrality measure to identify potential circular permutation sites.
- Tested the method on extensive experimental data from dihydrofolate reductase and other proteins.
Main Results:
- The 'closeness' measure significantly outperformed solvent accessibility in identifying residues suitable for circular permutation.
- Successfully predicted viable circular permutation sites across various protein positions.
- Demonstrated the efficacy of graph-theoretic measures in capturing residue interactions relevant to protein folding.
Conclusions:
- Graph-theoretic 'closeness' is a powerful predictor for designing viable circular protein variants.
- This approach has significant implications for developing split enzyme reporter systems and protein-protein interaction screening.
- The study highlights the utility of graph theory in understanding protein folding dynamics and residue interactions.
Related Concept Videos
01:34Woodward–Hoffmann Selection Rules and Microscopic Reversibility
Electrocyclic reactions, cycloadditions, and sigmatropic rearrangements are concerted pericyclic reactions that proceed via a cyclic transition state. These reactions are stereospecific and regioselective. The stereochemistry of the products depends on the symmetry characteristics of the interacting orbitals and the reaction conditions. Accordingly, pericyclic reactions are classified as either symmetry-allowed or symmetry-forbidden. Woodward and Hoffmann presented the selection criteria for...
02:53Conservative Site-specific Recombination and Phase Variation
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
01:16Olefin Metathesis Polymerization: Ring-Opening Metathesis Polymerization (ROMP)
Ring-opening metathesis polymerization or ROMP involves strained cycloalkenes as starting materials. The mechanism of ROMP proceeds by reacting cycloalkene with Grubbs catalyst to give metallacyclobutane intermediate which undergoes a ring-opening reaction to form new carbene. The new carbene reacts with another molecule of cycloalkene. Repetition of these steps leads to the formation of an unsaturated open-chain polymer product. All these steps are reversible, however, relieving the ring...
01:26Thermal and Photochemical Electrocyclic Reactions: Overview
Electrocyclic reactions are reversible reactions. They involve an intramolecular cyclization or ring-opening of a conjugated polyene. Shown below are two examples of electrocyclic reactions. In the first reaction, the formation of the cyclic product is favored. In contrast, in the second reaction, ring-opening is favored due to the high ring strain associated with cyclobutene formation.
01:17Pericyclic Reactions: Introduction
Pericyclic reactions are organic reactions that occur via a concerted mechanism without generating any intermediates. The reactions proceed through the movement of electrons in a closed loop to form a cyclic transition state, where rearrangement of the σ and π bonds yields specific products.
Pericyclic reactions can be classified into three categories: electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. Electrocyclic reactions and sigmatropic rearrangements are...
Pericyclic reactions can be classified into three categories: electrocyclic reactions, cycloaddition reactions, and sigmatropic rearrangements. Electrocyclic reactions and sigmatropic rearrangements are...
02:13Overview of Transposition and Recombination
Transposons make up a significant part of genomes of various organisms. Therefore, it is believed that transposition played a major evolutionary role in speciation by changing genome sizes and modifying gene expression patterns. For example, in bacteria, transposition can lead to conferring antibiotic resistance. Movement of transposable elements within the genetic pool of pathogenic bacteria can aid in transfer of antibiotic-resistant genetic elements. In eukaryotes, transposons can carry out...