Comparative footprinting of DNA-binding proteins.
BACKGROUND
Comparative modelling is a computational method used to tackle a variety of problems in molecular biology and biotechnology. Traditionally it has been applied to model the structure of proteins on their own or bound to small ligands, although more recently it has also been used to model protein-protein interfaces. This work is the first to systematically analyze whether comparative models of protein-DNA complexes could be built and be useful for predicting DNA binding sites.


RESULTS
First, we describe the structural and evolutionary conservation of protein-DNA interfaces, and the limits they impose on modelling accuracy. Second, we find that side-chains from contacting residues can be reasonably modeled and therefore used to identify contacting nucleotides. Third, the DNASITE protocol is implemented and different parameters are benchmarked on a set of 85 regulators from Escherichia coli. Results show that comparative footprinting can make useful predictions based solely on structural data, depending primarily on the interface identity with respect to the template used.


BACKGROUND
DNASITE code available on request from the authors.
Contreras-Moreira
Bruno
B
Programa de Genómica Computacional, Centro de Ciencias Genómicas, Universidad Nacional Autónoma de México, Av.Universidad, s/n, 62210 Cuernavaca, Morelos, México. contrera@ccg.unam.mx
Collado-Vides
Julio
J
D000465:Algorithms; D001665:Binding Sites; D003198:Computer Simulation; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D023302:Protein Footprinting / Q000379:methods*; D017422:Sequence Analysis, DNA / Q000379:methods*; D020539:Sequence Analysis, Protein / Q000379:methods*; D017385:Sequence Homology
D004268:DNA-Binding Proteins; D004247:DNA