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@article{557010,
author = {Fadrná, Eva and Špačková, Naděžda and Štefl, Richard and Koča, Jaroslav and Cheatham, Thomas E. and Šponer, Jiří},
article_location = {Bethesda, USA},
article_number = {1},
keywords = {molecular dynamics; G-DNA; free energy calculations; DNA loop geometries; LES; force fields},
language = {eng},
issn = {0006-3495},
journal = {Biophysical Journal},
title = {Molecular dynamics simulations of guanine quadruplex loops:Advances and force field limitations},
url = {http://www.biophysj.org/cgi/content/abstract/87/1/227},
volume = {87},
year = {2004}
}
TY - JOUR
ID - 557010
AU - Fadrná, Eva - Špačková, Naděžda - Štefl, Richard - Koča, Jaroslav - Cheatham, Thomas E. - Šponer, Jiří
PY - 2004
TI - Molecular dynamics simulations of guanine quadruplex loops:Advances and force field limitations
JF - Biophysical Journal
VL - 87
IS - 1
SP - 227-242
EP - 227-242
PB - Biophysical Society
SN - 00063495
KW - molecular dynamics
KW - G-DNA
KW - free energy calculations
KW - DNA loop geometries
KW - LES
KW - force fields
UR - http://www.biophysj.org/cgi/content/abstract/87/1/227
N2 - A computational analysis of d(GGGGTTTTGGGG)2 guanine quadruplexes containing both lateral and diagonal four-thymidine loops was carried out using Molecular Dynamics (MD) simulations in explicit solvent, Locally Enhanced Sampling (LES) simulations, systematic conformational search, and free energy Molecular Mechanics, Poisson Boltzmann, Surface Area calculations with explicit inclusion of structural monovalent cations. The study provides, within the approximations of the applied all-atom additive force field, a qualitatively complete analysis of the available loop conformational space. The results are independent of the starting structures. Major conformational transitions not seen in conventional MD simulations are observed when LES is applied. The favored LES structures consistently provide lower free energies (as estimated by MM-PBSA) than other structures. Unfortunately, the predicted optimal structure for the diagonal loop arrangement differs substantially from the atomic resolution experiments. This result is attributed to force field deficiencies, such as the potential misbalance between solute cation and solvent cation terms. The MD simulations are unable to maintain stable coordination of the monovalent cations inside the diagonal loops reported in recent X-ray study. The optimal diagonal and lateral loop arrangements appear to be close in energy though a proper inclusion of the loop monovalent cations could stabilize the diagonal architecture.
ER -
FADRNÁ, Eva, Naděžda ŠPAČKOVÁ, Richard ŠTEFL, Jaroslav KOČA, Thomas E. CHEATHAM and Jiří ŠPONER. Molecular dynamics simulations of guanine quadruplex loops:Advances and force field limitations. \textit{Biophysical Journal}. Bethesda, USA: Biophysical Society, 2004, vol.~87, No~1, p.~227-242. ISSN~0006-3495.
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