title: The transition mechanism of DNA overstretching: a microscopic view using molecular dynamics.
abstract: The overstretching transition in torsionally unconstrained DNA is studied by means of atomistic molecular dynamics simulations. The free-energy profile as a function of the length of the molecule is determined through the umbrella sampling technique providing both a thermodynamic and a structural characterization of the transition pathway. The zero-force free-energy profile is monotonic but, in accordance with recent experimental evidence, becomes two-state at high forces. A number of experimental results are satisfactorily predicted: (i) the entropic and enthalpic contributions to the free-energy difference between the basic (B) state and the extended (S) state; (ii) the longitudinal extension of the transition state and (iii) the enthalpic contribution to the transition barrier. A structural explanation of the experimental finding that overstretching is a cooperative reaction characterized by elementary units of approximately 22 base pairs is found in the average distance between adenine/thymine-rich regions along the molecule. The overstretched DNA adopts a highly dynamical and structurally disordered double-stranded conformation which is characterized by residual base pairing, formation of non-native intra-strand hydrogen bonds and effective hydrophobic screening of apolar regions.
authors.affiliation: Laboratory of Physiology, Department of Biology, University of Florence, Sesto Fiorentino, Firenze, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Bongini
authors.affiliation: Laboratory of Physiology, Department of Biology, University of Florence, Sesto Fiorentino, Firenze, Italy vincenzo.lombardi@unifi.it.
authors.forename: V
authors.initials: V
authors.lastname: Lombardi
authors.affiliation: Laboratory of Physiology, Department of Biology, University of Florence, Sesto Fiorentino, Firenze, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Bianco
mesh_terms: D055119:Elastic Modulus; D008956:Models, Chemical; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D044367:Phase Transition; D013314:Stress, Mechanical; D013718:Tensile Strength
keywords: DNA overstretching transition; molecular dynamics simulation of DNA overstretching; structural dynamics and energetics of DNA overstretching; structural model of DNA overstretching