EXIA2: web server of accurate and rapid protein catalytic residue prediction.

We propose a method (EXIA2) of catalytic residue prediction based on protein structure without needing homology information. The method is based on the special side chain orientation of catalytic residues. We found that the side chain of catalytic residues usually points to the center of the catalytic site. The special orientation is usually observed in catalytic residues but not in noncatalytic residues, which usually have random side chain orientation. The method is shown to be the most accurate catalytic residue prediction method currently when combined with PSI-Blast sequence conservation. It performs better than other competing methods on several benchmark datasets that include over 1,200 enzyme structures. The areas under the ROC curve (AUC) on these benchmark datasets are in the range from 0.934 to 0.968.