The Role of Water in Protein-DNA Recognition

Jayaram, B.; Jain, Tarun

doi:10.1146/annurev.biophys.33.110502.140414

Cited by 193 publications

(171 citation statements)

References 144 publications

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“…This mechanism is especially intriguing because sequence dependent hydration effects are already known to play a role in sequence dependent DNA-protein interactions (43) and RNA folding (44). It would be reasonable to assume that hydration effects also play a role in homology-dependent dsDNA/ dsDNA interaction and attractive to think that such diverse situations all have a common underlying physical basis.…”

Section: Discussionmentioning

confidence: 99%

Single molecule detection of direct, homologous, DNA/DNA pairing

Danilowicz¹,

Lee²,

Kim

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Using a parallel single molecule magnetic tweezers assay we demonstrate homologous pairing of two double-stranded (ds) DNA molecules in the absence of proteins, divalent metal ions, crowding agents, or free DNA ends. Pairing is accurate and rapid under physiological conditions of temperature and monovalent salt, even at DNA molecule concentrations orders of magnitude below those found in vivo, and in the presence of a large excess of nonspecific competitor DNA. Crowding agents further increase the reaction rate. Pairing is readily detected between regions of homology of 5 kb or more. Detected pairs are stable against thermal forces and shear forces up to 10 pN. These results strongly suggest that direct recognition of homology between chemically intact B-DNA molecules should be possible in vivo. The robustness of the observed signal raises the possibility that pairing might even be the ''default'' option, limited to desired situations by specific features. Protein-independent homologous pairing of intact dsDNA has been predicted theoretically, but further studies are needed to determine whether existing theories fit sequence length, temperature, and salt dependencies described here.dsDNA ͉ sequence-dependent P airing of homologous DNA/chromosome regions is a central feature of many biologically important processes. Recombinational double-strand break repair and programmed homologous recombination during meiosis all involve complex series of biochemical reactions in which single-stranded DNA (ssDNA) plays a prominent role. There also exist homologous pairing reactions that seem to involve interactions between chromosomal regions whose DNAs are chemically intact double-stranded DNA (dsDNA) (1-15). In some instances, whole chromosomes pair via multiple interactions all along their lengths (1-9) or via any region present in duplicate copies (10). In other cases, pairing occurs preferentially or exclusively in particular localized regions (''pairing sites''), which tend to involve repeated sequences, specific proteins (for establishment and/or maintenance of pairing) and/or heterochromatic regions (characterized by a paucity of genes and a less ''open'' chromatin structure) (1,(11)(12)(13)(14)(15).In contrast to recombination-related processes that are known to involve protein-mediated Watson-Crick basepairing interactions between a ssDNA and a ssDNA or dsDNA partner, the fundamental basis for ''recombination-independent'' pairing remains mysterious. The most obvious possibility is direct DNA/DNA interactions. Theoretical models have proposed that homology recognition arises from non-Watson-Crick hydrogen bond interactions between bases in the major or minor grooves (16). Local melting could also occur, permitting recognition via standard Watson-Crick base pairing. Other theories suggest that homology recognition can occur due to interactions between sequencedependent charge distributions associated with neighboring DNA helices, where the charge distributions include not only the phosphates in the DNA but also other ...

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Section: Discussionmentioning

confidence: 99%

Single molecule detection of direct, homologous, DNA/DNA pairing

Danilowicz¹,

Lee²,

Kim

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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“…In addition, it has been demonstrated that residues and bases not directly in contact with each other also can play important roles in protein-DNA recognition via various mechanisms, e.g. by water-mediated contacts 14 or sequence-dependent, binding-induced conformational changes and distortions. 15,16 Because of the great diversity of protein-DNA binding patterns and modes, identifying DNAbinding proteins based on structural features is a challenging task, especially if the goal is to devise a method that is not limited to a particular family of DNA-binding proteins, e.g.…”

Section: Introductionmentioning

confidence: 99%

Efficient Prediction of Nucleic Acid Binding Function from Low-resolution Protein Structures

Szilágyi

Skolnick

2006

Journal of Molecular Biology

152

168

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Structural genomics projects as well as ab initio protein structure prediction methods provide structures of proteins with no sequence or fold similarity to proteins with known functions. These are often low-resolution structures that may only include the positions of C a atoms. We present a fast and efficient method to predict DNA-binding proteins from just the amino acid sequences and low-resolution, C a -only protein models. The method uses the relative proportions of certain amino acids in the protein sequence, the asymmetry of the spatial distribution of certain other amino acids as well as the dipole moment of the molecule. These quantities are used in a linear formula, with coefficients derived from logistic regression performed on a training set, and DNA-binding is predicted based on whether the result is above a certain threshold. We show that the method is insensitive to errors in the atomic coordinates and provides correct predictions even on inaccurate protein models. We demonstrate that the method is capable of predicting proteins with novel binding site motifs and structures solved in an unbound state. The accuracy of our method is close to another, published method that uses all-atom structures, time-consuming calculations and information on conserved residues.

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“…2b). The role of these water molecules in protein-DNA recognition and complex formation is diverse as reviewed previously (Jayaram and Jain 2004). We classified the hydrogen bonded interfacial water molecules into those only contacting the DNA or those facilitating water-mediated contacts between amino acids and the DNA sugar-phosphate backbone or bases.…”

Section: Recovery Of Water-mediated Hydrogen Bonded Contactsmentioning

confidence: 99%

“…For protein-DNA interactions in particular, water molecules are involved in diverse tasks such as screening for favorable DNA interaction sites, stabilizing complex formation and facilitating specific interactions (Janin 1999;Jayaram and Jain 2004;Reddy et al 2001;Schwabe 1997). For example, the specificity in the trp repressor-operator complex is governed nearly exclusively by water-mediated amino acid to base interactions (Otwinowski et al 1988;Shakked et al 1994).…”

Section: Introductionmentioning

confidence: 99%

Solvated protein–DNA docking using HADDOCK

et al. 2013

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Interfacial water molecules play an important role in many aspects of protein-DNA specificity and recognition. Yet they have been mostly neglected in the computational modeling of these complexes. We present here a solvated docking protocol that 3 allows explicit inclusion of water molecules in the docking of protein-DNA complexes and demonstrate its feasibility on a benchmark of 30 high-resolution protein-DNA complexes containing crystallographically-determined water molecules at their interfaces. Our protocol is capable of reproducing the solvation pattern at the interface and recovers hydrogen-bonded water-mediated contacts in many of the benchmark cases. Solvated docking leads to an overall improvement in the quality of the generated protein-DNA models for cases with limited conformational change of the partners upon complex formation. The applicability of this approach is demonstrated on real cases by docking a representative set of 6 complexes using unbound protein coordinates, model-built DNA and knowledge-based restraints. As HADDOCK supports the inclusion of a variety of NMR restraints, solvated docking is also applicable for NMR-based structure calculations of protein-DNA complexes.4

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The Role of Water in Protein-DNA Recognition

Cited by 193 publications

References 144 publications

Single molecule detection of direct, homologous, DNA/DNA pairing

Single molecule detection of direct, homologous, DNA/DNA pairing

Efficient Prediction of Nucleic Acid Binding Function from Low-resolution Protein Structures

Solvated protein–DNA docking using HADDOCK

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