Protein-DNA binding specificity: a grid-enabled computational approach applied to single and multiple protein assemblies.
We use a physics-based approach termed ADAPT to analyse the sequence-specific interactions of three proteins which bind to DNA on the side of the minor groove. The analysis is able to estimate the binding energy for all potential sequences, overcoming the combinatorial problem via a divide-and-conquer approach which breaks the protein-DNA interface down into a series of overlapping oligomeric fragments. All possible base sequences are studied for each fragment. Energy minimisation with an all-atom representation and a conventional force field allows for conformational adaptation of the DNA and of the protein side chains for each new sequence. As a result, the analysis depends linearly on the length of the binding site and complexes as large as the nucleosome can be treated, although this requires access to grid computing facilities. The results on the three complexes studied are in good agreement with experiment. Although they all involve significant DNA deformation, it is found that this does not necessarily imply that the recognition will be dominated by the sequence-dependent mechanical properties of DNA.
Zakrzewska
Krystyna
K
Institut de Biologie et Chimie des Protéines, CNRS UMR 5086/Université de Lyon, 7 passage du Vercors, 69367 Lyon, France. k.zakrzewska@ibcp.fr
Bouvier
Benjamin
B
Michon
Alexis
A
Blanchet
Christophe
C
Lavery
Richard
R
D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D011485:Protein Binding; D051876:Sex-Determining Region Y Protein / Q000737:chemistry; D035181:TATA-Box Binding Protein / Q000737:chemistry; D013816:Thermodynamics
D004268:DNA-Binding Proteins; D051876:Sex-Determining Region Y Protein; D035181:TATA-Box Binding Protein; D004247:DNA