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Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
1000
HIPPO: HIstogram-based Pseudo-POtential for scoring protein-ssRNA fragment-based docking poses
Anna Kravchenko1, Sjoerd Jacob de Vries1, Malika Smaïl-Tabbone1
1Université de Lorraine, CNRS, Inria, LORIA, 54000, Nancy, France.
BMC Bioinformatics
|March 27, 2024
Summary
HIPPO, a new scoring potential, enhances the structural modeling of RNA-Recognition motif (RRM) and single-stranded RNA (ssRNA) interactions. This method improves upon existing techniques, making RRM-ssRNA complex prediction more accurate.
Area of Science:
- Structural biology
- Computational biology
- Bioinformatics
Background:
- RNA-Recognition motif (RRM) domains are crucial for binding single-stranded RNA (ssRNA) and are found in ~2% of the human genome.
- Studying RRM-ssRNA interactions is challenging due to ssRNA flexibility, limiting structural analysis.
- Current methods like ssRNA'TTRACT use ATTRACT, but its parameters are outdated and not ssRNA-specific.
Purpose of the Study:
- To develop an enhanced scoring potential for predicting the 3D structure of RRM-ssRNA complexes.
- To improve upon the accuracy and efficiency of existing ssRNA modeling techniques.
Main Methods:
- Developed HIPPO, a composite scoring potential derived from contact frequencies in docking models.
- HIPPO integrates four distinct potentials, each trained on protein-trinucleotide docking decoys.
- Scoring involves evaluating contact distances between RNA-protein coarse-grained beads based on frequency in correct vs. incorrect poses.
Main Results:
- HIPPO demonstrated a threefold or higher enrichment for half of the fragments in a benchmark of 57 RRM-ssRNA complexes.
- This represents a significant improvement over the ATTRACT scoring function, which achieved this enrichment for only a quarter of fragments.
- HIPPO drastically improved the likelihood of very high enrichment (12-fold or higher), crucial for modeling entire ssRNA chains.
Conclusions:
- HIPPO advances the state-of-the-art in RRM-ssRNA structural modeling.
- The approach shows potential for extension to other protein-nucleic acid interactions.
- Further research is needed to optimize HIPPO for direct practical application in modeling complete ssRNA chains.
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