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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
An automatic method for assessing structural importance of amino acid positions
Michael I Sadowski1, David T Jones
1Computer Science Department, University College London, Gower St, London, WC1E 6BT, UK. msadows@nimr.mrc.ac.uk
BMC Structural Biology
|March 6, 2009
Summary
This study quantifies the link between protein sequence conservation and changes in global tertiary structure. A novel correlation method identifies key residues critical for structural integrity, aiding in automated protein analysis.
Area of Science:
- Structural bioinformatics
- Computational biology
- Protein evolution
Background:
- Qualitative understanding of protein sequence-structure relationships exists.
- Quantitative analysis of sequence conservation's impact on tertiary structure changes was lacking.
Purpose of the Study:
- To quantitate the relationship between evolutionary sequence conservation and global tertiary structure changes.
- To demonstrate the suitability of Spearman correlation for this purpose.
Main Methods:
- Utilized Spearman correlation to analyze sequence and structural changes.
- Investigated the correlation between conservation at sequence positions and structural alterations.
Main Results:
- Identified specific residues (buried, bends, cysteines, prolines, leucines) significantly correlated with structural change.
- Found some buried residues, particularly in active sites, were less informative than expected.
Conclusions:
- The correlation-based method accurately predicts structurally important positions.
- This approach aligns with manual analyses and can enhance automated residue annotation pipelines.
- A PERL script for implementing the method is available.
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Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence.
The primary structure of a protein is its amino acid sequence.
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