Protein and molecular surfaces

Protein and molecular surfaces refer to the three-dimensional boundaries of a biomolecule that are accessible to solvent molecules or ligands. These surfaces are defined by the spatial arrangement of atoms and their associated physical properties, such as electrostatic potential and hydrophobicity, which govern how the molecule interacts with its biological environment [1][2]. In drug discovery, the characterization of these surfaces is a prerequisite for structure-based drug design, as it allows researchers to identify binding sites and predict the complementarity of potential drug candidates [3]. While every therapeutic target possesses a molecular surface, the term itself is a general structural concept rather than a specific protein, enzyme, or receptor [1]. Consequently, it does not have a specific biological function or disease role independent of the specific molecule being described. Modern approaches utilize geometric deep learning to map these surfaces, enabling the design of surface-mimetic drugs or the disruption of protein-protein interfaces [3]. Therefore, this entry represents a category of structural analysis rather than a distinct pharmacological target. [1] Lee, B., & Richards, F. M. (1971). The interpretation of protein structures: estimation of static accessibility. Journal of Molecular Biology. [2] Connolly, M. L. (1983). Analytical molecular surface calculation. Journal of Applied Crystallography. [3] Gainza, P., et al. (2020). Deciphering interaction fingerprints from protein molecular surfaces using geometric deep learning. Nature Methods.

Other names

Molecular surfaceSolvent-accessible surface (SAS)Van der Waals surfaceProtein interfaceExposed surface areaConnolly surface

Not applicable