Biomedical subjects

R Monasson

Publications and source records attributed to R Monasson.

12 recordsLinked to original sources

PubMed2006

Inference of DNA sequences from mechanical unzipping: an ideal-case study.

The performances of Bayesian inference to predict the sequence of DNA molecules from fixed-force unzipping experiments are investigated. We show that the probability of misprediction decreases exponentially with the amount of collected data. The decay rate is calculated as a function of biochemical parameters (binding free energies), the sequence content, the applied force, the elastic properties of a DNA single strand, and time resolution.

Bacteriophage lambda↗

PubMed2003

Rigorous decimation-based construction of ground pure states for spin-glass models on random lattices.

A constructive scheme for determining pure states at very low temperature in the 3-spins glass model on a random lattice is provided, in full agreement with Parisi's one step replica symmetry breaking (RSB) scheme. Proof is based on the analysis of a partial decimation procedure and of the statistical properties of its output, i.e., a reduced Hamiltonian acting on a subset of the initial spins. The number of ground states (GS) in each state, the number of states, and the distances between GS are calculated and correspond to RSB predictions.

Journal Article↗

PubMed2003

Slow nucleic acid unzipping kinetics from sequence-defined barriers.

Recent experiments on unzipping of RNA helix-loop structures by force have shown that approximately 40-base molecules can undergo kinetic transitions between two well-defined "open" and "closed" states, on a timescale approximately 1 sec [Liphardt et al., Science 297, 733-737 (2001)]. Using a simple dynamical model, we show that these phenomena result from the slow kinetics of crossing large free energy barriers which separate the open and closed conformations. The dependence of barriers on sequence along the helix, and on the size of the loop(s) is analyzed. Some DNA and RNA sequences that could show dynamics on different time scales, or three(or more)-state unzipping, are proposed. Our dynamical model is also applied to the unzipping of long (kilo-basepair) DNA molecules at constant force.

Base Pairing↗

PubMed2003

Force-extension behavior of folding polymers.

The elastic response of flexible polymers made of elements which can be either folded or unfolded, having different lengths in these two states, is discussed. These situations are common for biopolymers as a result of folding interactions intrinsic to the monomers, or as a result of binding of other smaller molecules along the polymer length. Using simple flexible-chain models, we show that even when the energy epsilon associated with maintaining the folded state is comparable to k(B) T, the elastic response of such a chain can mimic usual polymer linear elasticity, but with a force scale enhanced above that expected from the flexibility of the chain backbone. We discuss recent experiments on single-stranded DNA, chromatin fiber and double-stranded DNA with proteins weakly absorbed along its length which show this effect. Effects of polymer semiflexiblity and torsional stiffness relevant to experiments on proteins binding to dsDNA are analyzed. We finally discuss the competition between electrostatic self-repulsion and folding interactions responsible for the complex elastic response of single-stranded DNA.

Journal Article↗

PubMed2001

Force and kinetic barriers to unzipping of the DNA double helix.

A theory of the unzipping of double-stranded DNA is presented and is compared to recent micromanipulation experiments. It is shown that the interactions that stabilize the double helix and the elastic rigidity of single strands simply determine the sequence-dependent approximately 12-pN force threshold for DNA strand separation. Using a semimicroscopic model of the binding between nucleotide strands, we show that the greater rigidity of the strands when formed into double-stranded DNA, relative to that of isolated strands, gives rise to a potential barrier to unzipping. The effects of this barrier are derived analytically. The force to keep the extremities of the molecule at a fixed distance, the kinetic rates for strand unpairing at fixed applied force, and the rupture force as a function of loading rate are calculated. The dependence of the kinetics and of the rupture force on molecule length is also analyzed.

DNA↗

PubMed2001

Trajectories in phase diagrams, growth processes, and computational complexity: how search algorithms solve the 3-satisfiability problem.

Decision and optimization problems typically fall into one of two categories for any particular solving algorithm. The problem is either solved quickly (easy) or demands an impractically long computational effort (hard). Here we show that some characteristic parameters of problems can be tracked during a run of the algorithm defining a trajectory through the parameter space. Focusing on 3-satisfiability, a recognized representative of hard problems, we analyze trajectories generated by search algorithms. These trajectories can cross well-defined phases, corresponding to domains of easy or hard instances, and allow one to successfully predict the times of resolution.

Journal Article↗

PubMed1996