[sci.chem] Molecular Modeling

syswerda@bbn.com (Gilbert Syswerda) (12/05/90)

I am looking for the results of work people have done in the area of
predicting the chemical and physical properties of molecules. What would be
ideal is a program that could compute properties of a molecule based on its
formulation. The kind of information that would be useful is
hydrophobicity/philicity, electron withdrawing/donation,
aliphatic/aromatic, flexibility/rigidity, planar/non-planar (and other
topological features), and heterocyclic/non-heterocyclic. Properties of
molecules in solution would also be very useful.

The idea here is that there are large databases of molecules with known
interactions (e.g. binding rate at a receptor site in the nervous system).
Various techniques (e.g. ID3) could be applied to these databases to
construct classification schemes, and these could then be used to predict
the properties of new molecules. For this to work, a meaningful set of
parameters (like those listed above) must exist for each molecule. These
parameters are difficult and costly to obtain experimentally; it is usually
easier to simply try the molecule to see if it has the desired effect.

The parameters are also probably difficult to compute as well, but some are
easy (e.g. molecular weight). At any rate, I would like to find out what
can be computed today and what the general state-of-the-art is in this area.

fax0236@uoft02.utoledo.edu (12/06/90)

In article <61332@bbn.BBN.COM>, syswerda@bbn.com (Gilbert Syswerda) writes:
> I am looking for the results of work people have done in the area of
> predicting the chemical and physical properties of molecules. What would be
> ideal is a program that could compute properties of a molecule based on its
> formulation. The kind of information that would be useful is
> hydrophobicity/philicity, electron withdrawing/donation,
> aliphatic/aromatic, flexibility/rigidity, planar/non-planar (and other
> topological features), and heterocyclic/non-heterocyclic. Properties of
> molecules in solution would also be very useful.

You don't ask much.  Some of these are trivial to calculate, others don't
even need to be calculated (i.e. benzene is planar, you don't have to 
calculate that).  But almost nothing except molecular weight can be calculated
from molecular formula (not formulation).  The number of possible isomeric
structures of any system tends to be huge.  
> 
> The idea here is that there are large databases of molecules with known
> interactions (e.g. binding rate at a receptor site in the nervous system).
> Various techniques (e.g. ID3) could be applied to these databases to
> construct classification schemes, and these could then be used to predict
> the properties of new molecules. For this to work, a meaningful set of
> parameters (like those listed above) must exist for each molecule. These
> parameters are difficult and costly to obtain experimentally; it is usually
> easier to simply try the molecule to see if it has the desired effect.
> 
The kinds of data bases you are thinking of are readily available in the
literature (they may not be compiled lists, but certainly much of the data
is known and could be found with some library work) or in corporate
data bases (probably proprietary).  There would be no need to get much of
this data by repeating work, either experimentally or computationally.

> The parameters are also probably difficult to compute as well, but some are
> easy (e.g. molecular weight). At any rate, I would like to find out what
> can be computed today and what the general state-of-the-art is in this area.

State of the art is complex, since some things can be calculated with a 
high degree of precision and accuracy, some can only be estimated, and many
are not unique solutions.  Your best bet is to take two or three years to
study computational chemistry as a graduate student or post-doctoral fellow.
Even then, you will only learn a small fraction of the available methods.

Sorry if this sounds harsh, but you seem to have a vague idea of what might
be an interesting approach (although one that is certainly being pursued by
others right now) but you don't know enough yet to formulate the question
properly.  One person I know of who is doing a lot of this type of work
is Dr. George Famini at Aberdeen (the Army, for God's sakes!).  His work
involves using known physico-chemical data to develop models that allow
predictions of activity for many types of compounds.  I can provide his
e-mail address if you write to me.

Doug Smith
Assistant Professor of Chemistry
The University of Toledo
Toledo, OH  43606
FAX0236@UOFT02.UTOLEDO.EDU