Subject: Re: CCL:Question about Electrostatics in Molecular Mechanics

From: [email-masked] (David J. States)
Date: Fri, 18 Aug 1995 10:26:41 -0500

I worte:

>So if you really want to do the calculation correctly,
>electronic polarization, in addition to molecular reorientation, must
>be modeled explicitly.

and Jeffrey L. Nauss responded:
...
> However, I am not familiar with
> any empirical potential energy function that incorporates polarization
> except for that developed in Wilma Olson's group for nucleic acids
...

Sorry for the delay in replying.  There have been a few empirical potentials
published over the years with polarization terms.  Adler has done some noble
gas simulations and solvation of charged species in noble/vdW gasses and
liquids with models that incorporate polarization.  There is an ancient (early
70's) Stillinger water model that treated water as a gas of protons and
polarizable oxygens (interesting concept, but the resulting model had some
problems with fitting experimental data).  There is a second polarizable water
model from the same era for which I don't recall the authors (it was a Nature
article and focused on hydrogen bonding in liquid water).  Peter Kolman has
also published a polarizable water model (J.  Chem.  Phys., ?  early 80's).
Since this is not a field in which I am currently active, there may well have
been other, more recent, contributions to the literature.

The attraction of such models is that hydrogen bonding falls out in a very
natural way as 1/R**4 charge induced dipole and 1/R**6 dipole induced dipole
terms.

There seem to have been two major stumbling blocks to acceptance of these
models.  The first is compute time.  As part of every PE evaluation, you need
to do an iteration to self-consistency for the polarization terms.  Even though
this iteration usually converges pretty quickly, it multiplies the compute time
for a simulation by a factor or 3 to 10.  But now that the PC or Mac that you
use of wordprocessing is a hundred times faster than the VAX-11/780 on which we
ran the original protein molecular dynamics, I don't find this much of an
excuse.

The second, and perhaps more signficant, problem is one of parameterization.
It is clear that bonds and delocalized pi orbital systems have anisotropic
polarizations.  So you need 6 polarization parameters for every type of bond
in a model.  For a typical biomolecule, specifying all of these accurately
is a pretty duanting task.  Hence the focus on water models and monoatomic
gases.

As long as we are talking about electrostatics, let me get on another soap box:
titrable groups.  Essentially all biological macromolecules exists as an
equilibrium population of different titration states.  MD simulations based on
a
particular assignment of charges (or even uniformly scaled charges) will be
fundamentally flawed.  It would be interesting to see someone pickup the
Stillinger proton/oxygen gas model for water again.  The appeal of this
approach is that the protons are free to move from site to site so titration
can be realistically included in the simulation.  This is, afterall, a well
documented phenomenon occuring in aqueous solution on a picosecond time scale.

David

-- 
David J. States
Institute for Biomedical Computing / Washington University in St. Louis