title: Investigating dynamic and energetic determinants of protein nucleic acid recognition: analysis of the zinc finger zif268-DNA complexes.
abstract: BACKGROUND
  Protein-DNA recognition underlies fundamental biological processes ranging from transcription to replication and modification. Herein, we present a computational study of the sequence modulation of internal dynamic properties and of intraprotein networks of aminoacid interactions that determine the stability and specificity of protein-DNA complexes.
  
  
  RESULTS
  To this aim, we apply novel theoretical approaches to analyze the dynamics and energetics of biological systems starting from MD trajectories. As model system, we chose different sequences of Zinc Fingers (ZF) of the Zif268 family bound with different sequences of DNA. The complexes differ for their experimental stability properties, but share the same overall 3 D structure and do not undergo structural modifications during the simulations. The results of our analysis suggest that the energy landscape for DNA binding may be populated by dynamically different states, even in the absence of major conformational changes. Energetic couplings between residues change in response to protein and/or DNA sequence variations thus modulating the selectivity of recognition and the relative importance of different regions for binding.
  
  
  CONCLUSIONS
  The results show differences in the organization of the intra-protein energy-networks responsible for the stabilization of the protein conformations recognizing and binding DNA. These, in turn, are reflected into different modulation of the ZF's internal dynamics. The results also show a correlation between energetic and dynamic properties of the different proteins and their specificity/selectivity for DNA sequences. Finally, a dynamic and energetic model for the recognition of DNA by Zinc Fingers is proposed.
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, CNR, Via Mario Bianco 9, 20131 Milano, Italy.
authors.forename: Rubben
authors.initials: R
authors.lastname: Torella
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Moroni
authors.forename: Michele
authors.initials: M
authors.lastname: Caselle
authors.forename: Giulia
authors.initials: G
authors.lastname: Morra
authors.forename: Giorgio
authors.initials: G
authors.lastname: Colombo
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D051766:Early Growth Response Protein 1 / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D011485:Protein Binding; D011487:Protein Conformation; D013379:Substrate Specificity; D016335:Zinc Fingers
chemical_list: D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; D004247:DNA