PolyProline Predictor: A web server for empirical sequence-based prediction of polyproline II helices
Rubén López-Sánchez1, David Pantoja-Uceda1, Miguel Mompeán1
1Departamento de Química Física Biológica, Instituto de Química Física "Blas Cabrera"-CSIC, Madrid, Spain.
Summary
We developed PolyProline Predictor (PPP), a new tool to identify polyproline II (PPII) helices in proteins. PPP uses sequence similarity to experimentally validated structures, aiding the study of protein function and disorder.
Area of Science:
- Structural Biology
- Bioinformatics
- Protein Science
Background:
- Polyproline II (PPII) helices are crucial left-handed protein structures involved in molecular recognition and signaling.
- Predicting PPII helices from amino acid sequences is challenging due to subtle determinants and misclassification as random coil.
Purpose of the Study:
- To introduce PolyProline Predictor (PPP), a web server for sequence-based prediction of PPII helices.
- To provide an interpretable method for identifying PPII helix propensity, complementing machine learning approaches.
Main Methods:
- PPP aligns query sequences with a database of experimentally validated PPII helices.
- The server generates a similarity map sensitive to composition and position.
- Molecular dynamics simulations and biophysical techniques (CD, NMR) were used for validation.
Main Results:
- PPP identified conserved PPII motifs in known proteins and predicted them in uncharacterized regions, including glycine-rich proteins and virulence factors.
- The tool successfully predicted PPII conformations in regions modeled by AlphaFold and experimentally validated in RIPK3.
- Simulations and spectroscopy confirmed PPII structures in mycobacterial, plant, and RIPK3 proteins.
Conclusions:
- PPP offers a novel, interpretable approach to predict PPII helix propensity, filling a gap in bioinformatics tools.
- The findings expand the understanding of PPII helix roles in protein structure, function, and intrinsically disordered regions.
- This tool facilitates the exploration of PPII helices across proteomes, particularly in low-complexity regions.
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