The transition mechanism of DNA overstretching: a microscopic view using molecular dynamics.
J R Soc Interface
; 11(97): 20140399, 2014 Aug 06.
Article
em En
| MEDLINE
| ID: mdl-24920111
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Modelos Moleculares
/
Simulação de Dinâmica Molecular
/
Modelos Químicos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J R Soc Interface
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Itália