Biophysical Descriptor Distributions for Single Protein Domains and Inter-Domain Interactions

The hydrophobic fraction of proteins' solvent-accessible surface area (SASAH) is crucial for understanding various physical phenomena, particularly in protein-protein interactions and aggregation. However, assessing the relationships between different biophysical descriptors (e.g., protein size, surface charges, shape) and SASAH values can be challenging. This study explores SASAH values for functional protein domains and introduces a structural bioinformatics-based approach to estimate SASAH for non-redundant single-domain proteins. We evaluate the correlations of SASAH with descriptors such as protein mass, charge, radius of gyration, and secondary structure content. Additionally, we investigate the significance of sphericity and roughness, less commonly used descriptors, and analyse their relationships. Roughness is a complex parameter that is challenging to calculate due to the fact that surfaces can exhibit a wide range of textures and irregularities that vary across different scales and applications. Due to irregularities, multiple methods are used to calculate a surface's roughness. We compared the roughness descriptor values to the scores allocated by molecular docking algorithms to protein-protein interactions, highlighting its importance in molecular docking. All descriptors of protein biophysical properties, especially surface hydrophobicity, are essential for understanding molecular docking, as they modulate both protein-protein and protein-ligand interactions, providing deeper insights into the biophysical properties of proteins and their aggregates.