@Article{CiCP-13-223,
author = {Allyn R. Brice and Brian N. Dominy},
title = {Examining Electrostatic Influences on Base-Flipping: A Comparison of TIP3P and GB Solvent Models},
journal = {Communications in Computational Physics},
year = {2013},
volume = {13},
number = {1},
pages = {223--237},
abstract = {<p style="text-align: justify;">Recently, it was demonstrated that implicit solvent models were capable of
generating stable B-form DNA structures. Specifically, generalized Born (GB) implicit
solvent models have improved regarding the solvation of conformational sampling
of DNA [1, 2]. Here, we examine the performance of the GBSW and GBMV models
in CHARMM for characterizing base flipping free energy profiles of undamaged and
damaged DNA bases. Umbrella sampling of the base flipping process was performed
for the bases cytosine, uracil and xanthine. The umbrella sampling simulations were
carried-out with both explicit (TIP3P) and implicit (GB) solvent in order to establish the
impact of the solvent model on base flipping. Overall, base flipping potential of mean
force (PMF) profiles generated with GB solvent resulted in a greater free energy difference of flipping than profiles generated with TIP3P. One of the significant differences
between implicit and explicit solvent models is the approximation of solute-solvent
interactions in implicit solvent models. We calculated electrostatic interaction energies
between explicit water molecules and the base targeted for flipping. These interaction
energies were calculated over the base flipping reaction coordinate to illustrate the stabilizing effect of the explicit water molecules on the flipped-out state. It is known that
nucleic base pair hydrogen bonds also influenced the free energy of flipping since these
favorable interactions must be broken in order for a base to flip-out of the helix. The
Watson-Crick base pair hydrogen bond fractions were calculated over the umbrella
sampling simulation windows in order to determine the effect of base pair interactions
on the base flipping free energy. It is shown that interaction energies between the flipping base and explicit water molecules are responsible for the lower base flipping free
energy difference in the explicit solvent PMF profiles.</p>},
issn = {1991-7120},
doi = {https://doi.org/10.4208/cicp.210711.121011s},
url = {http://global-sci.org/intro/article_detail/cicp/7220.html}
}