InteracTor: A new integrative feature extraction toolkit for improved characterization of protein structural properties

Understanding the structural and functional diversity of protein families is crucial for elucidating their biological roles. Traditional analyses often focus on primary and secondary structures, which include amino acid sequences and local folding patterns like alpha helices and beta sheets. However, primary and secondary structures alone may not fully represent the complex interactions within proteins. To address this limitation, we developed a new algorithm (InteracTor) to analyze proteins by extracting features from their three-dimensional (3D) structures. The toolkit extracts interatomic interaction features such as hydrogen bonds, van der Waals interactions, and hydrophobic contacts, which are crucial for understanding protein dynamics, structure, and function. Incorporating 3D structural data and interatomic interaction features provides a more comprehensive understanding of protein structure and function, potentially enhancing downstream predictive modeling capabilities. By using the extracted features in Mutual Information scoring (MI), Principal Component Analysis (PCA), t-distributed Stochastic Neighbor Embedding (t-SNE), Uniform Manifold Approximation and Projection (UMAP), and hierarchical clustering analysis as use cases, we identified clear separations among protein structural families, highlighting distinct functional aspects. Our analysis revealed that interatomic interaction features were more informative than protein secondary structure features, providing insights into potential structural and functional properties. These findings underscore the significance of considering tertiary structure in protein analysis, offering a robust framework for future studies aiming at enhancing the capabilities of models for protein function prediction and drug discovery.