Subject: Summary: vdW parameters

From: Grzegorz Bakalarski <[email-masked]>
Date: Thu, 18 Jan 2001 10:55:28 +0100

Hello,

About week ago I asked:

> Recently I analyzed vdW parameters in different
> force fields
> (sybyl, few flavors from MSI, Charmm, MM3 etc) and I
> noticed
> that the parameters differ  substantially!
> In crystallografer community the most popular are
> Bondi vdW radii
> and they are in most cases completely different from
> those used in forcefields.
> The only exception is sybyl forcefield, but here
> also parameter for
> H atom is 1.5 A (instead of 1.2 A) which gives 0.6A
> difference for H-H
> interaction.
> My question is: what is origin of these (huge)
> differences ? Physical
> origin of the vdW is known and should not change
> from forcefield to
> forcefield ...
> In a case of overlapping H-H pair a repulsive force
> calculated using
> sybyl vdW radii is substantial, (e.g. if distance is
> 2.5A) but using
> Bondi's radii the force  is small and even
> attracting

Here are responses I've got. Thanks again to all for valuable
discussion.

G.Bakalarski

+++++++++++++++++++
*From: "Michael K. Gilson" <[email-masked]>

The variation in H-bond radii may come in part from the fact
that most current force-fields model hydrogen bonds in
terms of electrostatics (Coulomb's law) + vdw interactions.
In order to get a good strong H-bond, the radius of a polar
H must be artificially reduced so the H's positive charge
can get close to the H-bond acceptor.  If you need a reference
for this, let me know and I'll dig one up.

Regards,
Mike Gilson

++++++++++++++++++++
*From: Marvin Waldman <[email-masked]>
With regard to your CCL question below about differences in vdW parameters,
it has been found that the parameters can be quite sensitive to various
factors such as the form of the potential function (e.g. exp-6, LJ 12-6, LJ
9-6, ...), the form of the combination rules used for mixed parameters, the
charge model used, and most importantly, the type of data used to fit the
parameters (e.g. crystal structures, liquid simulations, ...).  Also, the
parameters will be correlated with the torsional parameters of a force
field as both are generally involved in determining vicinal (1-4)
interactions.  As such, the parameters indeed do tend to vary quite
substantially.  The vdW parameters are _not_ experimental_
observables.  Rather, they are part of an overall model (the force field)
which is used to predict/fit various experimental results.  Depending on
the particular types of experiment you are trying to predict/fit and the
rest of the force field model, the vdW parameters themselves can be quite
different.  Discussion of some of these points can be found in the
following references:

Z.Peng, C.S. Ewig, M.-J. Hwang, M. Waldman, A.T. Hagler, J.Phys.Chem. A,
vol. 101, pp. 7243-7252 (1997)

C.S. Ewig, T.S. Thacher, A.T. Hagler, J.Phys.Chem. B, vol. 103, pp.
6998-7014 (1999)

Regards,

Marvin Waldman, Ph.D.
Senior Director, Rational and Combinatorial Drug Design
Molecular Simulations Inc.

++++++++++++++++++++++
*From: [email-masked] (Alan Shusterman)
--- You wrote:
what is origin of these (huge) differences ?
--- end of quote ---
Your question is a good one. The answer turns out to be fairly simple, but it has several parts.

First, the vdW parameters used by force fields (FF) are designed to reproduce geometries of
+particular molecules selected by the FF developer. The identities of these molecules vary from one
+developer to the next, so the target data is not the same for all FF.

Also, one can think of a FF as having two parts, the vdW part and everything else. The "everything
+else" part varies from one FF to the next, so even if two FF tried to reproduce the same molecular
+geometries they would have to use different "vdW" parameters to get there. (What is more, different
+FF often use different equations to model vdW interactions, so different kinds of parameters are
+required for this reason.)

It also needs to be recognized that most FF are not designed to reproduce the data that so-called
+experimental vdW radii are based on. Most (but not all) FF try to reproduce the geometries of
+isolated molecules. Experimental vdW radii come from a variety of sources, but they generally
+reflect some type of intermolecular interaction, and these interactions may contain more than vdW
+interactions. As a result, comparing experimental and FF vdW parameters (and energies) may be
+nonsensical.

I hope this helps. You might consult Allinger's book, "Molecular Mechanics", for a more detailed
+explanation.

-Alan

+++++++++++++++
*From: Rick Venable <[email-masked]>

One issue may be the exact meaning of the "radii"; CHARMM radii
represent the minimum of a Leonard-Jones 6-12 potential, while other
force fields (like Merck) may use a somewhat different interpretion, as
well as additional terms.  You really have to look at the underlying
equations used to explictly compute the VDW energy, and not just the
radii.

Although the physical basis for VDW may be understood as a diffusive
interaction of the electron clouds which may have some long range
character, most force fields use a simple Morse or LJ curve to model
this interaction, which is mostly a short range approximation of the
real VDW forces.

--
Rick Venable    

+++++++++++++++
*From: Irilenia Nobeli <[email-masked]>

Dear Grzegorz,
 
Force fields are commonly empirically fitted which means that the van der
Waals parameters are allowed to vary until  the value of some
property(ies) that depends on them agrees with either experimental or ab
initio results.
Hence although these parameters are normally restricted to some
"acceptable" values, the optimum fitted values are unlikely to be
identical to what one would expect from Bondi radii, the most common
reason for this being that they have to absorb other inaccuracies in the
potential, e.g. approximations to the dispersion energy by R6 terms and
neglect of other terms such as polarisation energy.
 
Hope this helps.
 
Irilenia
 
------------------------------------------------
Irene (Irilenia) Nobeli
Biomolecular Structure and Modelling Unit
Department of Biochemistry and Molecular Biology
University College London

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