Analyzing protein-DNA recognition mechanisms.
We present a computational algorithm that can be used to analyze the generic mechanisms involved in protein-DNA recognition. Our approach is based on energy calculations for the full set of base sequences that can be threaded onto the DNA within a protein-DNA complex. It is able to reproduce experimental consensus binding sequences for a variety of DNA binding proteins and also correlates well with the order of measured binding free energies. These results suggest that the crystal structure of a protein-DNA complex can be used to identify all potential binding sequences. By analyzing the energy contributions that lead to base sequence selectivity, it is possible to quantify the concept of direct versus indirect recognition and to identify a new concept describing whether the protein-DNA interaction and DNA deformation terms select optimal binding sites by acting in accord or in disaccord.
Paillard
Guillaume
G
Laboratoire de Biochimie Théorique, CNRS UPR 9080, Institut de Biologie Physico-Chimique, 13 rue Pierre et Marie Curie, Paris 75005, France.
Lavery
Richard
R
D000465:Algorithms; D001483:Base Sequence; D001665:Binding Sites; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004268:DNA-Binding Proteins / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation
D004268:DNA-Binding Proteins