Exploiting a reduced set of weighted average features to improve prediction of DNA-binding residues from 3D structures.

Predicting DNA-binding residues from a protein three-dimensional structure is a key task of computational structural proteomics. In the present study, based on machine learning technology, we aim to explore a reduced set of weighted average features for improving prediction of DNA-binding residues on protein surfaces. Via constructing the spatial environment around a DNA-binding residue, a novel weighting factor is first proposed to quantify the distance-dependent contribution of each neighboring residue in determining the location of a binding residue. Then, a weighted average scheme is introduced to represent the surface patch of the considering residue. Finally, the classifier is trained on the reduced set of these weighted average features, consisting of evolutionary profile, interface propensity, betweenness centrality and solvent surface area of side chain. Experimental results on 5-fold cross validation and independent tests indicate that the new feature set are effective to describe DNA-binding residues and our approach has significantly better performance than two previous methods. Furthermore, a brief case study suggests that the weighted average features are powerful for identifying DNA-binding residues and are promising for further study of protein structure-function relationship. The source code and datasets are available upon request.