Modeling multi-component protein-DNA complexes: the role of bending and dimerization in the complex of p53 dimers with DNA

Protein Eng. 2001 Apr;14(4):233-43. doi: 10.1093/protein/14.4.233.

Abstract

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.

MeSH terms

  • Binding Sites
  • DNA / chemistry*
  • DNA / metabolism
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Dimerization
  • Humans
  • Models, Molecular*
  • Molecular Conformation
  • Oligonucleotides / chemistry
  • Oligonucleotides / metabolism
  • Static Electricity
  • Thermodynamics
  • Tumor Suppressor Protein p53 / chemistry
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • DNA-Binding Proteins
  • Oligonucleotides
  • Tumor Suppressor Protein p53
  • DNA