Hoogsteen base pairs proximal and distal to echinomycin binding sites on DNA

Forms of the DNA double helix containing non-Watson-Crick base-pairing have been discovered recently based on x-ray diffraction analysis of quinoxaline antibiotic-oligonucleotide complexes. In an effort to find evidence for Hoogsteen base-pairing at quinoxaline-binding sites in solution, chemical "footprinting" (differential cleavage reactivity) of echinomycin bound to DNA restriction fragments was examined. We report that purines (A>G) in the first and/or fourth base-pair positions of occupied echinomycin-binding sites are hyperreactive to diethyl pyrocarbonate. The correspondence of the solid-state data and the sites of diethyl pyrocarbonate hyperreactivity suggests that diethyl pyrocarbonate may be a sensitive reagent for the detection of Hoogsteen base-pairing in solution. Moreover, a 12-base-pair segment of alternating A-T DNA, which is 6 base pairs away from the nearest strong echinomycin-binding site, is also hyperreactive to diethyl pyrocarbonate in the presence of echinomycin. This hyperreactive segment may be an altered form of right-handed DNA that is entirely Hoogsteen base-paired

Ground state and glass transition of the RNA secondary structure

RNA molecules form a sequence-specific self-pairing pattern at low temperatures. We analyze this problem using a random pairing energy model as well as a random sequence model that includes a base stacking energy in favor of helix propagation. The free energy cost for separating a chain into two equal halves offers a quantitative measure of sequence specific pairing. In the low temperature glass phase, this quantity grows quadratically with the logarithm of the chain length, but it switches to a linear behavior of entropic origin in the high temperature molten phase. Transition between the two phases is continuous, with characteristics that resemble those of a disordered elastic manifold in two dimensions. For designed sequences, however, a power-law distribution of pairing energies on a coarse-grained level may be more appropriate. Extreme value statistics arguments then predict a power-law growth of the free energy cost to break a chain, in agreement with numerical simulations. Interestingly, the distribution of pairing distances in the ground state secondary structure follows a remarkable power-law with an exponent -4/3, independent of the specific assumptions for the base pairing energies

The effect of RNA stiffness on the self-assembly of virus particles

Under many in vitro conditions, some small viruses spontaneously encapsidate a single stranded (ss) RNA into a protein shell called the capsid. While viral RNAs are found to be compact and highly branched because of long distance base-pairing between nucleotides, recent experiments reveal that in a head-to-head competition between a ssRNA with no secondary or higher order structure and a viral RNA, the capsid proteins preferentially encapsulate the linear polymer! In this paper, we study the impact of genome stiffness on the encapsidation free energy of the complex of RNA and capsid proteins. We show that an increase in effective chain stiffness because of base-pairing could be the reason why under certain conditions linear chains have an advantage over branched chains when it comes to encapsidation efficiency. While branching makes the genome more compact, RNA base-pairing increases the effective Kuhn length of the RNA molecule, which could result in an increase of the free energy of RNA confinement, that is, the work required to encapsidate RNA, and thus less efficient packaging

Stringent Nucleotide Recognition by the Ribosome at the Middle Codon Position.

Accurate translation of the genetic code depends on mRNA:tRNA codon:anticodon base pairing. Here we exploit an emissive, isosteric adenosine surrogate that allows direct measurement of the kinetics of codon:anticodon University of California base formation during protein synthesis. Our results suggest that codon:anticodon base pairing is subject to tighter constraints at the middle position than at the 5'- and 3'-positions, and further suggest a sequential mechanism of formation of the three base pairs in the codon:anticodon helix

Triplet Superconductors from the Viewpoint of Basic Elements for Quantum Computers

We discuss possibilities of utilizing superconductors with Cooper condensates in triplet pairing states (where the spin of condensate pairs is S=1) for practical realization of quantum computers. Superconductors with triplet pairing condensates have features that are unique and cannot be found in the usual (singlet pairing, S=0) superconductors. The symmetry of the order parameter in some triplet superconductors (e.g., ruthenates) corresponds to doubly-degenerate chiral states. These states can serve as qubit base states for quantum computing.Comment: 4 pages, 5 figures, will be presented at ASC-2002 and submitted to IEEE Trans. Appl. Supercon