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Extensive explicit-solvent molecular dynamics simulations are used for examining the allosteric mechanism of the catabolite activator protein (CAP). A new mechanism is proposed by which CAP has triggered the transcription activation that is based on an order to disorder transition mediated by cyclic adenosine monophosphate (cAMP) binding as well as DNA.

The DNA-DNA and DNA-drug interactions are quantitatively characterized by angle-resolved surface plasmon resonance (SPR) imaging, by directly measuring DNA and drug surface coverages and kinetics simultaneously for multiple patterned spots. DNA-DNA hybridization kinetics and thermodynamics measured by the imaging system and the traditional SPR are in excellent agreement and the kinetics of actinomycin-D binding to a low-density DNA binding sequence is measured.

NMR is used for describing the structure-function relationship on desamido-bacitracin (Bc) of low antibiotic activity, wherein D-Glu-4 is shown to be vital for the bioactivity of Bc. The interaction of the phosphor-moiety with Bc is reflected by DNA binding, wherein metal-free Bc does not bind DNA, whereas various metal complexes of Bc do and Cu(II)_Bc is shown to bind and oxidatively cleave DNA under reduction conditions in the air.

A genetically encoded fluorescent copper(I) sensor based on the copper(I)-binding-induced conformational change of a copper-responsive transcriptional regulator is described. The reporter Amt1-FRET has operated in the dynamic range of the cellular copper buffer in mammalian cells, reported dynamic fluctuations of the cellular copper availability within minutes of perturbation and has visualized the tightly controlled copper availability in mammalian cells.

The use of silicon chips with 16 DNA-modified electrodes (DME chips) utilizing DNA-mediated charge transport for multiplexed detection of DNA and DNA-binding protein targets is described. The results have shown how DME chips have facilitated sensitive and selective detection of DNA and DNA-binding protein targets in a robust and internally standardized multiplexed format.

The conformational and physical properties of the disordered C-terminal domain of TAR DNA-binding protein 43 (TDP-43) are clarified by preparing many peptide fragments and showing that only D1 within D1-4 has formed twisted fibrils with a cross section under the incubation of phosphate buffer. The studies have shown that all the three peptides formed an amyloid structure, which has provided insights into the nature of its aggregation with regard to the other fragments in the C-terminus of TDP-43.

Max-47 is a designed hybrid protein that comprises of the Max DNA-binding basic region and E47 HLH dimerization subdomain. Modified yeast one-hybrid system (Y1H) is used for showing that Max-E47 has outcompeted the native MaxbHLHZ for the E-box and these hybrids have provided a minimalist scaffold for exploring the relationship between protein structure and DNA-binding function.

Cyclic 8-ring Py-Im polyamides have targeted the DNA-sequence 5'-WGWWCW-3', which has corresponded to the androgen response element (ARE) bound by the androgen receptor transcription factor to modulate gene expression. The studies have shown that cyclic Py-Im polyamides bind DNA with high affinities and regulate the expression of AR target genes in cell culture studies, which shows that the cycle is cell permeable.

The eukaryotic ssDNA binding protein, Replication Protein A (RPA) is used to demonstrate the application of NMR spectroscopy as a powerfull tool to characterize the remodeling of architecture in different functional states of modular proteins with multiple domains. The first direct evidence obtained for the remodeling of RPA upon binding ssDNA, including an alteration in the availability of the RPA32N domain might help explain damage-dependent phosphorylation in modular proteins.

A new method is used for measuring forces between small protein domains based on double electron-electron resonance (DEER) spectroscopy by using a model peptide derived from the [alpha]-helical coiled-coil leucine zipper of yeast transcriptional activator GCN4. The equilibrium distribution of distances between two nitroxide spin labels rigidly attached to the helices of the dimer is determined by using DEER and has produced a closing force of 100[plusmn]10 pH between monomers.

Extensive replica exchange (REX) simulations are carried out in an optimized generalized Born (GB) force field to characterize the disordered states of a regulatory intrinsically disordered protein (IDP), KID domain of transcription factor CREB and its phosphorylated form, pKID. The results have shown that an implicit solvent-based modeling framework, despite various existing limitations, is feasible for accurate atomistic simulation of small IDPs.

The studies have shown that derivatives of wrenchnolol, a synthetic molecule that interacts with Sur-2 coactivator, serve as activation modules and stimulate gene transcription in vitro and in cells when tethered to a DNA-binding molecule. Thirteen derivatives of wrenchnolol are chemically prepared, optimized and tested for their ability to activate transcription in vitro and in cells.

The screening of a compound library of synthetic DNA binding molecules for selective binding to the consensus sequence of the transcription factor LEF-1 followed by the assessment of the candidate compounds in a series of assays has provided two lead compounds, lefmycin-2 and lefmycin-2. The sequence of screens defining the method has assured that activity in the final functional assay is directly related to the inhibition of gene transcription and DNA binding properties of the molecules.

The stereoselective synthesis of subglutinols A and B and the potential of subglutinol A as an immunosuppressive drug with dose-dependent osteogenic activity are described. Activating protein 1 (AP-1) family transcription factors are one of the key regulators for the anabolic activity of subglutinol A.

An unusual tricyclic adduct as the major product obtained from oxidation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (dOG) in the presence of tyrosine (Tyr) or its analogue p-cresol is reported. The oxidation reactions have significant implications in the chemical nature of DNA-protein cross-links derived from oxidative stress.

A rapid and sensitive electrochemical assay is used for the electrochemical detection of nanomolar TATA-binding protein (TBP) binding to DNA in the presence of other proteins. This method is based on an interruption of DNA-mediated electrochemistry associated with protein binding and hence can be applied in detecting other proteins that perturb the DNA base stack.

The cooperative binding interactions between the L-Enantiomers of transition state analogue inhibitors and the human purine nucleoside phosphorylase (PNP) are discussed.

The nonequilibrium synthesis of Cu2O nanoparticles is accomplished using an engineered derivative of the DNA-binding protein Tral in a room-temperature precursor electrolyte. The results show that a protein with no intrinsic inorganic synthesis activity can be endowed with the ability to control the formation of inorganic nanostructures under thermodynamically unfavorable conditions, reproducing a key feature of biological hard-tissue growth and assembly.

The design of sequence-specific fluorescent double-stranded DNA (dsDNA)-binding oligomers by incorporating multiple 6-5 fused dimer recognition modules is reported. Sequence-specific DNA binding molecules containing a fluorescent switch integrated as part of the recognition module can be used to detect DNA sequences without denaturation and in the absence of conjugation to a dye molecule.

A colorimetric assay, which could screen for potential triple helix specific DNA binders and simultaneously determine their relative binding affinities using DNA-functionalized Au nanoparticles is described. The developed colorimetric assay is able to determine triplex relative binding capabilities by monitoring color change, which allowed dramatically improved discrimination between stabilizing and nonstabilizing triplex binders.

A study reports an alternative method for generating metal-mediated base pairs in deoxyribonucleic acid (DNA) duplexes using only naturally occurring pyrimidine bases. Thymine-thymine (T--T) mispairs in DNA duplexes selectively capture Hg(super II) ions, and the metal-meidated thymine-Hg(super II)-thymine base pairs form in DNA duplexes.

A molecular beacon (MB) is designed, synthesized and investigated using locked nucleic acid (LNA) bases. The high thermostability, the enhanced selectivity and the ability of the MB-LNA probe to resist nuclease digestion and binding of single-stranded DNA binding protein (SSB), make it critically important for biological applications.