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Optimization of Synthetic Proteins: Identification of Interpositional Dependencies Indicating Structurally and/or Functionally Linked Residues
Published on: July 14, 2015
Looking for a sequence based allostery definition: a statistical journey at different resolution scales
Saritha Namboodiri1, Alessandro Giuliani, Achuthsankar S Nair
1State Inter University Centre of Excellence in Bioinformatics, University of Kerala, Kariyavattom Campus, Thiruvananthapuram, Kerala, India.
Journal of Theoretical Biology
|April 10, 2012
Summary
This study identifies key protein signatures for allosteric regulation using computational analysis. Hydrophobicity patterns in protein sequences effectively predict allosteric behavior and conformational changes with high accuracy.
Area of Science:
- Biophysics
- Computational Biology
- Protein Science
Background:
- Allosteric regulation is crucial for protein function, involving conformational changes distant from the binding site.
- Identifying allosteric sites and understanding transmission mechanisms remain challenging.
- Protein sequence features may encode information about allosteric regulation.
Purpose of the Study:
- To detect allosteric hotspot signatures that drive global conformational changes.
- To computationally assess the interaction strength between allosteric sites.
- To establish hydrophobicity patterning as a determinant of allostery.
Main Methods:
- Employed a co-evolution model and free-energy-transfer hydrophobicity scale (Tanford scale).
- Utilized Cross-Recurrence Quantification Analysis (Cross-RQA) on allosteric sequences.
- Compared allosteric proteins against random and generic protein sets using Recurrence Quantification Analysis (RQA).
Main Results:
- Cross-RQA revealed strong interactions among allosteric susceptible sites, possibly via transient weak bonds.
- Hydrophobicity patterning, quantified by RQA descriptors, was confirmed as a determinant of allostery.
- Free-energy-transfer hydrophobicity-based RQA markers are specific to allosteric signatures.
- Pattern recognition tools distinguished allosteric proteins with 92% accuracy using these markers.
Conclusions:
- Hydrophobicity patterning in protein sequences is a significant determinant of allosteric regulation.
- The developed RQA markers provide a robust method for identifying allosteric proteins.
- This approach enhances our understanding of allosteric mechanisms and conformational changes.
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