title: Detecting cis-regulatory binding sites for cooperatively binding proteins.
abstract: Several methods are available to predict cis-regulatory modules in DNA based on position weight matrices. However, the performance of these methods generally depends on a number of additional parameters that cannot be derived from sequences and are difficult to estimate because they have no physical meaning. As the best way to detect cis-regulatory modules is the way in which the proteins recognize them, we developed a new scoring method that utilizes the underlying physical binding model. This method requires no additional parameter to account for multiple binding sites; and the only necessary parameters to model homotypic cooperative interactions are the distances between adjacent protein binding sites in basepairs, and the corresponding cooperative binding constants. The heterotypic cooperative binding model requires one more parameter per cooperatively binding protein, which is the concentration multiplied by the partition function of this protein. In a case study on the bacterial ferric uptake regulator, we show that our scoring method for homotypic cooperatively binding proteins significantly outperforms other PWM-based methods where biophysical cooperativity is not taken into account.
authors.affiliation: Department of Electrical Engineering, ESAT-SCD, Katholieke Universiteit Leuven, Kasteelpark Arenberg 10, 3001 Leuven, Belgium. Liesbeth.vanOeffelen@esat.kuleuven.be
authors.forename: Liesbeth
authors.initials: L
authors.lastname: van Oeffelen
authors.forename: Pierre
authors.initials: P
authors.lastname: Cornelis
authors.forename: Wouter
authors.initials: W
authors.lastname: Van Delm
authors.forename: Fedor
authors.initials: F
authors.lastname: De Ridder
authors.forename: Bart
authors.initials: B
authors.lastname: De Moor
authors.forename: Yves
authors.initials: Y
authors.lastname: Moreau
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry; D001665:Binding Sites; D004247:DNA / Q000737:chemistry; D004268:DNA-Binding Proteins / Q000378:metabolism; D008958:Models, Molecular; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011550:Pseudomonas aeruginosa / Q000235:genetics; D012097:Repressor Proteins / Q000737:chemistry; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C068477:ferric uptake regulating proteins, bacterial; D004247:DNA