Are predicted structures good enough to preserve functional sites?

Background: A principal goal of structure prediction is the elucidation of function. We have studied the ability of computed models to preserve the mi croenvironments of functional sites. In particular, 653 model structures of a calcium-binding protein (generated using an ab initio folding protocol) were analyzed, and the degree to which calcium-binding sites were recogniza ble was assessed. Results: While some model structures preserve the calcium-binding microenvi ronments, many others, including some with low root mean square deviations (rmsds) from the crystal structure of the native protein, do not. There is a very weak correlation between the overall rmsd of a structure and the pre servation of calcium-binding sites. Only when the quality of the model stru cture is high (rmsd less than 2 Angstrom for atoms in the 7 Angstrom local neighborhood around calcium) does the modeling of the binding sites become reliable. Conclusions: Protein structure prediction methods need to be assessed in te rms of their preservation of functional sites. High-resolution structures a re necessary for identifying binding sites such as calcium-binding sites.