Efficient prediction of nucleic acid binding function from low-resolution protein structures.
Structural genomics projects as well as ab initio protein structure prediction methods provide structures of proteins with no sequence or fold similarity to proteins with known functions. These are often low-resolution structures that may only include the positions of C alpha atoms. We present a fast and efficient method to predict DNA-binding proteins from just the amino acid sequences and low-resolution, C alpha-only protein models. The method uses the relative proportions of certain amino acids in the protein sequence, the asymmetry of the spatial distribution of certain other amino acids as well as the dipole moment of the molecule. These quantities are used in a linear formula, with coefficients derived from logistic regression performed on a training set, and DNA-binding is predicted based on whether the result is above a certain threshold. We show that the method is insensitive to errors in the atomic coordinates and provides correct predictions even on inaccurate protein models. We demonstrate that the method is capable of predicting proteins with novel binding site motifs and structures solved in an unbound state. The accuracy of our method is close to another, published method that uses all-atom structures, time-consuming calculations and information on conserved residues.
Center of Excellence in Bioinformatics, University at Buffalo, State University of New York, 901 Washington St, Buffalo, NY 14203, USA.
András
A
Szilágyi
Jeffrey
J
Skolnick
D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism*; D011485:Protein Binding
D004268:DNA-Binding Proteins