Accurate Prediction of Protein Catalytic Residues by Side Chain Orientation and Residue Contact Density

Abstract

Prediction of protein catalytic residues provides useful information for the studies of protein functions. Most of the existing methods combine both structure and sequence information but heavily rely on sequence conservation from multiple sequence alignments. The contribution of structure information is usually less than that of sequence conservation in existing methods. We found a novel structure feature, residue side chain orientation, which is the first structure-based feature that achieves prediction results comparable to that of evolutionary sequence conservation. We developed a structure-based method, Enzyme Catalytic residue SIde-chain Arrangement (EXIA), which is based on residue side chain orientations and backbone flexibility of protein structure. The prediction that uses EXIA outperforms existing structure-based features. The prediction quality of combing EXIA and sequence conservation exceeds that of the state-of-the-art prediction methods. EXIA is designed to predict catalytic residues from single protein structure without needing sequence or structure alignments. It provides invaluable information when there is no sufficient or reliable homology information for target protein. We found that catalytic residues have very special side chain orientation and designed the EXIA method based on the newly discovered feature. It was also found that EXIA performs well for a dataset of enzymes without any bounded ligand in their crystallographic structures.

iCataly-PseAAC: Identification of Enzymes Catalytic Sites Using Sequence Evolution Information with Grey Model GM (2,1)

“…Meanwhile, we can see that the To further approve its power, let's compare iCatalyPseAAC with the existing predictor in this area. Predictor CRpred (Zhang et al 2008) is based on sequence predictor, method EXIA (Chien and Huang 2012) is based on the residue side chain structure and sequence conservation method. Because our predictor is only one with a publicly accessible web server, the best way to compare them is though practical application.…”

“…To promote the biological community, a web server of iCataly-PseAAC was constructed, which can be freely accessible at http://www.jcibioinfo.cn/iCataly-PseAAC. (Zhang et al 2008) b From (Chien and Huang 2012) c From (Petrova and Wu 2006;Youn et al 2007) …”

EXIA2: Web Server of Accurate and Rapid Protein Catalytic Residue Prediction

“…Among the three residues, each residue receives a feature score S : $\begin{array}{c}S=w_n+z_j^w+z_j^a,\end{array}$ where w n is the averaged WCN, z j w is the normalized WCN of residue j , and z j a is the normalized amino acid combination score of residue j . The amino acid combination score is based on statistics of the amino acids of catalytic sites in the PW79 dataset [37]. For each type of amino acid, a profile p x containing 20 elements is constructed: $\begin{array}{c}{p}_x=\left(p_x^{\text{ALA}},p_x^{\text{CYS}},p_x^{\text{GLY}},\dots ,p_x^{\text{VAL}}\right),\end{array}$ where p x denotes the profile of amino acid type x ; each element in the profile is the frequency of an amino acid type appearing in the same catalytic site as amino acid type x .…”

Characterization and Identification of Protein S-Nitrosylation Sites Based on Tertiary Structures

“…The side chain orientation is an important indicator to determine a catalytic site on protein structure. Chien et al have used this method to predict protein catalytic residues [24]. According to their study, catalytic residue is a residue whose distance to the catalytic central is less than 10Å and side chain angle to catalytic central is less than 80 degree.…”