Subject: Re: CCL:MEP similarity

From: David Wild <[email-masked]>
Date: Thu, 19 Jun 1997 11:30:06 +0100

Fred Oooms ([email-masked]) wrote:
 > Dear netters
 > I would like to compare similarities between MEP of different
 > molecules and also to compare the MEP obtained by different methods
 > for the same compound. Which are the similarity index to be used to
 > do this kind of job. Any assistance would be appreciated. Thanks
 > Fred

The usual way (but not by any means only way) of doing this is to use
something like the Carbo Index:
 
( integral (PaPb) dv) / ( integral(Pa*Pa)dv**0.5 * integral(Pb*Pb)dv**0.5)

or the Hodgkin Index:

(2*integral (Pa*Pb)dv) / (integral(Pa*Pa)dv + integral (Pb*Pb)dv)

Where Pa and Pb are the MEP functions for the molecules a and b 
resprectively. These integrate the MEP over volume to create a field, 
and effectively calculate the overlap between the fields of the two 
molecules to produce a single similarity measure.

Good & Richards describe a way of quickly evaluating this integral 
using Gaussian approximations. Calculating the overlap requires that 
the molecules are first aligned so their fields overlay optimally. 
This may be done manually or automatically - a vairety of programs
are available to do this. We have developed one called FBSS which
can align molecules and calculate MEP (and now also shape and 
hydrophobic) similarity between them.

Useful papers to read are Good, A.C., J. Mol. Graphics, 1992, Vol 10,
144-151 (similarity measures), Good, A.C., Richards, W.G., J. Chem. 
Inf. Comput. Sci, 1993, 33, 112-116 (gaussian method), Wild, D.J., 
Willett, P., J. Chem. Inf. Comput. Sci 1996, 36, 159-167 and 
Thorner, D.A., Wild, D.J, Willett, P., Wright, P.M., J. Chem. Inf. 
Comput. Sci., 1996, 36, 900-908 (FBSS) 

Hope this is of some use!

David

__________________________________________________

Dr. David Wild, Computational Chemistry Group,
Department of Information Studies, University of
Sheffield, Sheffield S10 2TN, U.K.

Tel +44-(0)114 22 22669, Fax +44-(0)114 278 0300
Email [email-masked] 
http://www.shef.ac.uk/uni/academic/I-M/is/research/cisrg/davewild.html