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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Optimal contact map alignment of protein-protein interfaces
Vinay Pulim1, Bonnie Berger, Jadwiga Bienkowska
1Computer Science and Artificial Intelligence Laboratory, MIT, MIT, Cambridge, USA.
Bioinformatics (Oxford, England)
|August 20, 2008
Summary
CMAPi accurately aligns protein complex interfaces by analyzing contact maps, improving the identification of interacting residues, especially in low-similarity proteins. This enhances predictions of protein-protein interactions (PPIs).
Area of Science:
- Computational biology
- Structural bioinformatics
- Protein-protein interactions (PPIs)
Background:
- Protein structure alignment is crucial for identifying homologous residues and understanding protein function.
- Aligning protein complexes and their interfaces is a critical, yet challenging, next step.
- Existing methods often struggle with conformational changes and low sequence similarity.
Purpose of the Study:
- To introduce CMAPi, a novel algorithm for optimal alignment of protein complex interfaces.
- To develop a method that is more tolerant to conformational changes than existing techniques.
- To improve the accuracy of identifying interacting residues within protein families.
Main Methods:
- Developed CMAPi, a two-dimensional dynamic programming algorithm.
- Utilized a contact map representation of protein interfaces.
- Applied the algorithm to protein complexes from the SCOPPI database and cytokine families.
Main Results:
- CMAPi produces polynomial-time near-optimal alignments for multiple complexes.
- Demonstrated superior accuracy in aligning interacting residues compared to existing methods, particularly for low-similarity sequences.
- The contact map approach showed greater tolerance to conformational changes, aligning more of the interaction surface.
Conclusions:
- CMAPi offers a significant advancement in aligning protein complex interfaces.
- Improved interface alignments enhance homology modeling and threading for PPI prediction.
- The method provides a basis for generating template profiles for sequence-structure alignment.
Related Concept Videos
02:04Protein-protein Interfaces
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a polypeptide...
02:04Protein-Protein Interfaces
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01:49Conserved Binding Sites
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Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally analyses the...
01:24Protein Organization
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The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.
02:26Protein Networks
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These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
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01:57Protein Complexes with Interchangeable Parts
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