Fractal Dimensions of Macromolecular Structures

Quantifying the properties of macromolecules is a prerequisite for understanding their roles in biochemical processes. One of the less-explored geometric features of macromolecules is molecular surface irregularity, or 'roughness', which can be measured in terms of fractal dimension ( D). In this study, we demonstrate that surface roughness correlates with ligand binding potential. We quantified the surface roughnesses of biological macromolecules in a large-scale survey that revealed D values between 2.0 and 2.4. The results of our study imply that surface patches involved in molecular interactions, such as ligand-binding pockets and protein-protein interfaces, exhibit greater local fluctuations in their fractal dimensions than 'inert' surface areas. We expect approximately 22% of a protein's surface outside of the crystallographically known ligand binding sites to be ligandable. These findings provide a fresh perspective on macromolecular structure and have considerable implications for drug design as well as chemical and systems biology.