Modeling multi-component protein-DNA complexes: the role of bending and dimerization in the complex of p53 dimers with DNA.
We used molecular modeling to study the optimal conformation of the complex between two p53 DNA-binding domain monomers and a 12 base-pair target DNA sequence. The complex was constructed using experimental data on the monomer binding conformation and a new approach to deform the target DNA sequence. Combined with an internal/helicoidal coordinate model of DNA, this approach enables us to bend the target sequence in a controlled way while respecting the contacts formed with each p53 monomer. The results show that the dimeric complex favors DNA bending towards the major groove at the dimer junction by a value close to experimental findings. In contrast to inferences from earlier models, the calculation of key contributions to the free energy of the complexes indicates a determinant role for DNA in the formation of the complex with the dimer of the p53 DNA-binding domains.
Lebrun
A
A
Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York, NY 10029, USA.
Lavery
R
R
Weinstein
H
H
D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D019281:Dimerization; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism; D055672:Static Electricity; D013816:Thermodynamics; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism
D004268:DNA-Binding Proteins; D009841:Oligonucleotides; D016159:Tumor Suppressor Protein p53; D004247:DNA