Identification of DNA-binding proteins using structural, electrostatic and evolutionary features.
DNA-binding proteins (DBPs) participate in various crucial processes in the life-cycle of the cells, and the identification and characterization of these proteins is of great importance. We present here a random forests classifier for identifying DBPs among proteins with known 3D structures. First, clusters of evolutionarily conserved regions (patches) on the surface of proteins were detected using the PatchFinder algorithm; earlier studies showed that these regions are typically the functionally important regions of proteins. Next, we trained a classifier using features like the electrostatic potential, cluster-based amino acid conservation patterns and the secondary structure content of the patches, as well as features of the whole protein, including its dipole moment. Using 10-fold cross-validation on a dataset of 138 DBPs and 110 proteins that do not bind DNA, the classifier achieved a sensitivity and a specificity of 0.90, which is overall better than the performance of published methods. Furthermore, when we tested five different methods on 11 new DBPs that did not appear in the original dataset, only our method annotated all correctly. The resulting classifier was applied to a collection of 757 proteins of known structure and unknown function. Of these proteins, 218 were predicted to bind DNA, and we anticipate that some of them interact with DNA using new structural motifs. The use of complementary computational tools supports the notion that at least some of them do bind DNA.
Nimrod
Guy
G
Department of Biochemistry, The George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv 69978, Israel.
Szilágyi
András
A
Leslie
Christina
C
Ben-Tal
Nir
N
D000465:Algorithms; D019843:Archaeal Proteins / Q000737:chemistry / Q000235:genetics; D001409:Bacillus cereus / Q000737:chemistry / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000145:classification / Q000235:genetics*; D030562:Databases, Protein; D019143:Evolution, Molecular; D008958:Models, Molecular; D011487:Protein Conformation; D040901:Proteomics / Q000706:statistics & numerical data; D012680:Sensitivity and Specificity; D012984:Software; D055672:Static Electricity; D048229:Sulfolobus solfataricus / Q000737:chemistry / Q000235:genetics
D019843:Archaeal Proteins; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins