Chemistry Reference
In-Depth Information
features in the KBIs as a function of composition, namely aggregation of MOH
at low
x
MOH
. Here, we also argue that FFs that reproduce the composition depen-
dence of the KBIs for Ben + MOH mixtures are also more likely to correctly model
the behavior of both solvent-exposed and buried phenylalanine. NMA was chosen
because it is often used as a model for the peptide group. Low NMA compositions
were studied because they are more representative of physiological protein backbone
concentrations than high NMA compositions would appear. The current composi-
tions may very roughly mimic peptide-peptide interactions in the presence of large
amounts of water and may be very loosely analogous to the peptide interactions pres-
ent in the denatured state. Finally, zwitterionic Gly (
aq
) was chosen because, despite
being electrically neutral as a whole, Gly contains features similar to a mixture of
salt-bridge forming ions. All of these choices were also driven by the availability of
the required experimental data.
The analysis of the experimental data has been presented by us before
(Weerasinghe and Smith 2005; Kang and Smith 2006; Gee 2010; Ploetz and Smith
2011a; Karunaweera et al. 2012). All simulations were performed using classical
MD techniques and the GROMACS 4.5.3 simulation package (Hess et al. 2008). The
systems involved cubic simulation cells of 10 nm in length simulated for 100 ns of
production in the
NpT
ensemble. Further technical details can be found in our pre-
vious work (see Table 5.1) and will be supplemented in a future publication, which
will additionally expand the set of thermodynamic and physical properties com-
pared across the FFs. Note that perfect agreement with our previous results is not
TABLE 5.1
Currently Completed Kirkwood-Buff Derived Force Field (KBFF) Models
Solute
Solvent
Relevant Species
Reference
Acetone
Water
Cosolvent
(Weerasinghe and Smith 2003b)
Urea
Water
Cosolvent
(Weerasinghe and Smith 2003c)
NaCl
Water
Cosolvent
(Weerasinghe and Smith 2003d)
Guanidinium chloride
Water
Cosolvent, Arg
(Weerasinghe and Smith 2004)
Methanol
Water
Ser
(Weerasinghe and Smith 2005)
Amides
Water
Asn, Gln, peptide
group, blocked
termini
(Kang and Smith 2006)
Thiols, sulfides
Methanol
Met, Cys, disulfide
(Bentenitis, Cox, and Smith 2009)
Aromatics, aromatic
alcohols
Methanol
Phe, Tyr
(Ploetz and Smith 2011a)
Heterocycles
Methanol
or Water
Trp, His (charged and
neutral)
(Ploetz and Smith 2011a)
1º, 2º, 3º alcohols
Water
Thr, cosolvent
(Jiao et al. 2012)
Amine salts,
carboxylates
Water
Charged: Lys, Asp,
Glu, termini
(Gee and Smith 2012)
Amines, carboxylic acids
Water
Cosolvent, Neutral:
Lys, Asp, Glu, termini
(Dai, Weerasinghe, and Smith
2012)
