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Exploring Sequence Space to Identify Binding Sites for Regulatory RNA-Binding Proteins
Published on: August 9, 2019
Predicting target DNA sequences of DNA-binding proteins based on unbound structures
Chien-Yu Chen1, Ting-Ying Chien, Chih-Kang Lin
1Department of Bio-Industrial Mechatronics Engineering, National Taiwan University, Taipei, Taiwan.
Plos One
|February 8, 2012
Summary
Predicting DNA-binding protein targets from unbound structures is challenging but feasible. This study uses structure alignment to create synthetic complexes, enabling accurate prediction of DNA sequences even without co-crystallized structures.
Area of Science:
- Structural Biology
- Bioinformatics
- Computational Biology
Background:
- DNA-binding proteins (DBPs) are crucial for gene regulation, and predicting their target DNA sequences (often as position weight matrices, PWMs) is vital for understanding biological processes.
- Current methods successfully predict PWMs using knowledge-based potentials on protein-DNA co-crystallized structures.
- However, predicting target sequences for DBPs lacking co-crystallized structures remains a significant challenge.
Purpose of the Study:
- This study investigates the feasibility of predicting DNA sequences bound by DBPs using only their unbound structures.
- The research aims to develop and evaluate a novel method for generating accurate PWMs from unbound protein structures.
Main Methods:
- The proposed method utilizes structure alignment between an unbound query protein and a template complex to generate synthetic protein-DNA complexes.
- An atomic-level knowledge-based potential function is then applied to these synthetic complexes to predict PWMs.
- The approach was validated using seven DBPs with both bound and unbound structures and known PWMs.
Main Results:
- The study successfully predicted PWMs for DBPs using their unbound structures by generating synthetic complexes.
- Conformational changes in proteins upon DNA binding were identified as a key factor influencing prediction accuracy.
- The method demonstrates the potential of structure alignment-based approaches for predicting DNA-binding specificities.
Conclusions:
- Predicting target DNA sequences from unbound protein structures is achievable, offering a valuable alternative when co-crystallized structures are unavailable.
- The findings highlight the importance of considering protein conformational changes in prediction models.
- This work encourages further development of structure alignment-based methods for generating synthetic complexes in computational structural biology.
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