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 microenvironments 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 recognizable was assessed.


RESULTS
While some model structures preserve the calcium-binding microenvironments, 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 preservation of calcium-binding sites. Only when the quality of the model structure is high (rmsd less than 2 A for atoms in the 7 A local neighborhood around calcium) does the modeling of the binding sites become reliable.


CONCLUSIONS
Protein structure prediction methods need to be assessed in terms of their preservation of functional sites. High-resolution structures are necessary for identifying binding sites such as calcium-binding sites.
Stanford Medical Informatics, Stanford University School of Medicine, CA 94305-5479, USA.
L
L
Wei
E S
ES
Huang
R B
RB
Altman
D000818:Animals; D001665:Binding Sites; D002417:Cattle; D003198:Computer Simulation; D007413:Intestinal Mucosa / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D064030:S100 Calcium Binding Protein G / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014807:Vitamin D / Q000494:pharmacology
D064030:S100 Calcium Binding Protein G; D014807:Vitamin D