Binding similarity network of ligand.

The protein and ligand interaction takes an important part in protein function. Both ligand and its binding site are essential components for understanding how the protein-ligand complex functions. Until now, there have been many studies about protein function and evolution, but they usually lacked ligand information. Accordingly, in this study, we tried to answer the following questions: how much ligand and binding site are associated with protein function, and how ligands themselves are related to each other in terms of binding site. To answer the questions, we presented binding similarity network of ligand. Through the network analysis, we attempted to reveal systematic relationship between the ligand and binding site. The results showed that ligand binding site and function were closely related (conservation ratio, 81%). We also showed conservative tendency of function in line with ligand structure similarity with some exceptional cases. In addition, the binding similarity network of ligand revealed scale-free property to some degree like other biological networks. Since most nodes formed highly connected cluster, a clustering coefficient was very high compared with random. All the highly connected ligands (hubs) were involved in various functions forming large cluster and tended to act as a bridge between modular clusters in the network.