Subject: Re: CCL:NCI SMILES Database

From: <[email-masked]>
Date: Fri, 12 Sep 97 17:33:57 EDT

>>Marc C. Nicklaus & Bruno Bienfait raised an interesting point...  It
>>is difficult to do string comparisons with SMILES...  Does anyone know 
>>of any utilities available that can do this quickly and painlessly?
>
>Sure. The CACTVS toolkit programs (which was used to create one of
>the datasets) can read and compare SMILES-encoded structures.
>
>Note however that this is not a string-level comparison but
>operates on the decoded structures. Therefore, it is several
>magnitudes slower than simple string matching (but probably
>still fast enough for most applications).

ChemOffice can do this as well, so I did (and yes, it is *much* slower 
than text matching -- a little over 100 SMILES pairs per minute).

For the first 1000 entries, 26 were structurally different between the 
SMILES strings generated by CACTVS and those generated by Babel.  In 
each case, those generated by CACTVS were superior (which would have 
been my guess before starting, anyway).  Of the differences, 23 involved 
charged structures, which Babel neutral-ized.  Additionally, Babel seems 
not to be real fond of mercury atoms.

Other differences include different aromaticity-perception algorithms.  
The algorithm used by CACTVS is closer to the one used by Daylight.  
However, since the SMILES spec defines the delocalized (c1ccccc1) as 
absolutely equivalent to the Kekule version (C1=CC=CC=C1), this is not a 
big deal.  For that matter, it's not really clear why either program 
bothers to attempt aromaticity perception if they're not doing Unique 
SMILES.  I guess it looks nice, but as far as the SMILES definition 
goes, it's not relevent.

>Since SMILES strings are *not* unique, this can be a problem (several 
>possible strings for any given structure). I would suggest using SLN 
>strings instead. I know the ones in SYBYL are unique, I think others 
>may be too (ChemDraw? for example).

SLN strings come in unique and non-unique versions, just as do SMILES strings.  ChemDraw generates non-unique versions for both.

Ideally, NCI will provide the raw connection tables for this new data set, as they did several years ago for their 127,000-compound collection.  Each format conversion has potential for introducing problems, so the fewer, the better.

Jonathan Brecher
CambridgeSoft Corporation
[email-masked]