Biomedical Engineering Reference
In-Depth Information
23.3.2 Polarizable Continuum Models
It is possible in principle to define and determine the cavity from a straightforward
ab
initio
/DFT calculation by defining a molecular isodensity level outside which electron
density is treated as negligible. Such calculations are possible within Gaussian 03 but
literature applications are rare (presumably because of the expense).
The generally accepted compromise between computer resource and accuracy is based
on the definition of the cavity as a superposition of interlocked atomic spheres with radii
near the van der Waals radius. Our key reference is the review by Tomasi
et al.
(2005),
which builds on the oft-quoted review by Tomasi and Persico (1994).
For example, we might want to investigate the geometry and molecular properties of
phenylanine in different solvents using the PCMmodel. Here is a suitable Gaussian 03 .gjf:
%chk=d:\phenopt.chk
# B3LYP/6-311G
∗∗
scrf=(pcm,solvent=dichloromethane) opt freq
# geom=check
L-phenylanine PCM model
01
I have not shown the output for lack of space, but if you care to run the job then everything
will be instantly recognizable, including the optimized geometry and final energy.
23.4 Periodic Solvent Box
In Langevin dynamics and continuum models, the solvent is simulated; no solvent
molecules are explicitly included in the calculation. Such calculations give little micro-
scopic detail.
I mentioned the interest in water as solvent in earlier chapters, and it is worth reading
the abstract to Jorgensen's (1983) landmark Monte Carlo paper:
Classical Monte Carlo simulations have been carried out for liquid water in the NPT ensemble
at 25
◦
C and 1 atm using six of the simpler intermolecular potential functions for the water
dimer: Bernal-Fowler (BF), SPC, ST2, TIPS2, TIP3P and TIP4P. Comparisons are made
with experimental thermodynamic and structural data including the recent neutron diffraction
data of Thiessen and Narten. The computed densities and potential energies are in reasonable
accord with experiment except for the original BF model, which yields an 18% overestimate
of the density and poor structural results. The TIPS2 and TIP4P potentials yield oxygen-
oxygen partial structure functions in good agreement with the neutron diffraction results. The
accord with the experimental OH and HH partialstructure functions is poorer; however, the
computed results for these functions are similar for all the potential functions. Consequently,
the discrepancy may be due to the correction terms needed in processing the neutron data
or to an effect uniformly neglected in the computations. Comparisons are also made for self-
diffusion coefficients obtained frommolecular dynamics simulations. Overall, the SPC, SDT2,
TIPS2 and TIP4Pmodels give reasonable structural and thermodynamic descriptions of liquid
water and they should be useful in simulations of aqueous solutions. The simplicity of the
SPC, TIPS2, and TIP4P is also attractive from a computational standpoint.
