Energetics of the protein-DNA-water interaction

Spyrakis, Francesca; Cozzini, Pietro; Bertoli, Chiara; Marabotti, Anna; Kellogg, Glen E.; Mozzarelli, Andrea
January 2007
BMC Structural Biology;2007, Vol. 7, p4
Academic Journal
Background: To understand the energetics of the interaction between protein and DNA we analyzed 39 crystallographically characterized complexes with the HINT (Hydropathic INTeractions) computational model. HINT is an empirical free energy force field based on solvent partitioning of small molecules between water and 1-octanol. Our previous studies on protein-ligand complexes demonstrated that free energy predictions were significantly improved by taking into account the energetic contribution of water molecules that form at least one hydrogen bond with each interacting species. Results: An initial correlation between the calculated HINT scores and the experimentally determined binding free energies in the protein-DNA system exhibited a relatively poor r2 of 0.21 and standard error of ± 1.71 kcal mol-1. However, the inclusion of 261 waters that bridge protein and DNA improved the HINT score-free energy correlation to an r2 of 0.56 and standard error of ± 1.28 kcal mol-1. Analysis of the water role and energy contributions indicate that 46% of the bridging waters act as linkers between amino acids and nucleotide bases at the protein-DNA interface, while the remaining 54% are largely involved in screening unfavorable electrostatic contacts. Conclusion: This study quantifies the key energetic role of bridging waters in protein-DNA associations. In addition, the relevant role of hydrophobic interactions and entropy in driving protein-DNA association is indicated by analyses of interaction character showing that, together, the favorable polar and unfavorable polar/hydrophobic-polar interactions (i.e., desolvation) mostly cancel.


Related Articles

  • Two faces of water. Chandler, David // Nature;5/30/2002, Vol. 417 Issue 6888, p491 

    Focuses on the occurrence of hydrogen bonding in oil and water molecules. Segregation of oil-like amino acid from water; Concept of hydrophobic interaction; Identification of the hydrogen atoms of water molecules.

  • Optical Methods to Study Protein-DNA Interactions in Vitro and in Living Cells at the Single-Molecule Level. Monico, Carina; Capitanio, Marco; Belcastro, Gionata; Vanzi, Francesco; Pavone, Francesco S. // International Journal of Molecular Sciences;Feb2013, Vol. 14 Issue 2, p3961 

    The maintenance of intact genetic information, as well as the deployment of transcription for specific sets of genes, critically rely on a family of proteins interacting with DNA and recognizing specific sequences or features. The mechanisms by which these proteins search for target DNA are the...

  • Local Gene Regulation Details a Recognition Code within the Lacl Transcriptional Factor Family. Camas, Francisco M.; Alm, Eric J.; Poyatos, Juan F. // PLoS Computational Biology;Nov2010, Vol. 6 Issue 11, p1 

    The specific binding of regulatory proteins to DNA sequences exhibits no clear patterns of association between amino acids (AAs) and nucleotides (NTs). This complexity of protein-DNA interactions raises the question of whether a simple set of wide-coverage recognition rules can ever be...

  • DNA Cross-Linking by Dehydromonocrotaline Lacks Apparent Base Sequence Preference. Rieben Jr., W. Kurt; Coulombe Jr., Roger A. // Toxicological Sciences;Dec2004, Vol. 82 Issue 2, p497 

    Pyrrolizidine alkaloids (PAs) are ubiquitous plant toxins, many of which, upon oxidation by hepatic mixed-function oxidases, become reactive bifunctional pyrrolic electrophiles that form DNA-DNA and DNA-protein cross-links. The anti-mitotic, toxic, and carcinogenic action of PAs is thought to be...

  • PDA: an automatic and comprehensive analysis program for protein-DNA complex structures. RyangGuk Kim; Jun-tao Guo // BMC Genomics;2009 Supplement 1, Vol. 10, p1 

    Background: Knowledge of protein-DNA interactions at the structural-level can provide insights into the mechanisms of protein-DNA recognition and gene regulation. Although over 1400 protein-DNA complex structures have been deposited into Protein Data Bank (PDB), the structural details of...

  • From Nonspecific DNA-Protein Encounter Complexes to the Prediction of DNA-Protein Interactions. Mu Gao; Skolnick, Jeffrey // PLoS Computational Biology;Apr2009, Vol. 5 Issue 4, p1 

    DNA-protein interactions are involved in many essential biological activities. Because there is no simple mapping code between DNA base pairs and protein amino acids, the prediction of DNA-protein interactions is a challenging problem. Here, we present a novel computational approach for...

  • Cross-Genome Comparisons of Newly Identified Domains in Mycoplasma gallisepticum and Domain Architectures with Other Mycoplasma species. Chilamakuri, Chandra Sekhar Reddy; Joshi, Adwait; Rani, Sane Sudha; Offmann, Bernard; Sowdhamini, R. // Comparative & Functional Genomics;2011, Special section p1 

    Accurate functional annotation of protein sequences is hampered by important factors such as the failure of sequence search methods to identify relationships and the inherent diversity in function of proteins related at low sequence similarities. Earlier, we had employed intermediate sequence...

  • Amino acid residues in Rag1 crucial for DNA hairpin formation. Lu, Catherine P.; Sandoval, Hector; Brandt, Vicky L.; Rice, Phoebe A.; Roth, David B. // Nature Structural & Molecular Biology;Nov2006, Vol. 13 Issue 11, p1010 

    The Rag proteins carry out V(D)J recombination through a process mechanistically similar to cut-and-paste transposition. Specifically, Rag complexes form DNA hairpins through direct transesterification, using a catalytic Asp-Asp-Glu (DDE) triad in Rag1. How is sufficient DNA distortion...

  • Dynamic properties of water around a protein-DNA complex from molecular dynamics simulations. Sinha, Sudipta Kumar; Bandyopadhyay, Sanjoy // Journal of Chemical Physics;10/7/2011, Vol. 135 Issue 13, p135101 

    Formation of protein-DNA complex is an important step in regulation of genes in living organisms. One important issue in this problem is the role played by water in mediating the protein-DNA interactions. In this work, we have carried out atomistic molecular dynamics simulations to explore the...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics