Characterization of Local Geometry of Protein Surfaces with the Visibility Criteria

The visibility used in !VisGrid is defined as the fraction of visible directions from a target position on a protein surface. A pocket or a hollow is recognized as a cluster of positions with a small visibility. A large protrusion in a protein structure is recognized as a pocket in the negative image of the structure. !VisGrid correctly identified 95.0% of ligand-binding sites as one of the three largest pockets in 5616 benchmark proteins.

To examine how natural flexibility of proteins affects pocket identification, !VisGrid was tested on distorted structures by molecular dynamics simulation. Sensitivity decreased approximately 20% for structures of a root mean square deviation of 2.0 A to the original crystal structure, but specificity was not much affected. Because of its intuitiveness and simplicity, the visibility criterion will lay the foundation for characterization and function annotation of local shape of proteins.</p>