Proteinlerde bulunan ligand bağlanma yerlerinin ağ yapı modeli kullanarak tespit edilmesi

Biomolecular interactions play key roles in biological activity. Investigation of those interactions, including protein-ligand interactions, is crucial for understanding the way that nature designed its biological machinery. Ligand binding particularly requires, recognition of the ligand by the protein, which in turn arranges the three dimensional structure of the protein, mostly directed by the energetic interactions involved. Based on these requirements, ligand-binding has been considered as a local process. Yet, it has been recently shown that ligand binding depends not on the local structure, but rather on an interaction pathway, that takes part in rearrangement of the protein into the most favorable conformation upon binding.The nonlocal nature of the protein-ligand binding problem is investigated via the Gaussian Network Model with which the residues lying along interaction pathways in a protein and the residues at the binding site are predicted. The predictions of the binding site residues are verified by using several benchmark systems where the topology of the unbound protein and the bound protein-ligand complex are known. Predictions are made on the unbound protein. Agreement of results with the bound complexes indicates that the information for binding resides in the unbound protein. Cliques that consist of three or more residues that are far apart along the primary structure but are in contact in the folded structure are shown to be important determinants of the binding problem.Comparison with known structures shows that the predictive capability of the method is significant.