So much to do, so little time

Trying to squeeze sense out of chemical data

Archive for the ‘qsar’ tag

CDKDescUI Updates – DnD & Batch Mode

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I’ve put out an updated version (1.0.1) of the CDK descriptor calculator that now supports drag ‘n drop of the input file – just drag an appropriate file onto the UI and the input file text field should be automatically populated. In addition, all file dialogs let OS X users specify a file name manually.

The current version also supports a, frequently requested, command line batch mode. It’s a little limited compared to the GUI since you can’t specify individual descriptors, only descriptor categories (such as ‘all’, ‘topological’ etc) and the only output format is tab delimited.

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$ java -jar CDKDescUI.jar -h

usage: cdkdescui [OPTIONS] inputfile
                 
 -b    Batch mode
 -h    Help
 -o    Output file
 -t    Descriptor type: all, topological, geometric, constitutional,
       electronic, hybrid
 -v    Verbose output

CDKDescUI v1.0.1 Rajarshi Guha <rajarshi.guha@gmail.com>

By default, output is dumped to output.txt and all descriptors are evaluated. If errors occur for a given molecule and descriptor they are reported at the end (i.e., the program continues)

Written by Rajarshi Guha

April 4th, 2010 at 5:01 pm

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CDKDescUI Update

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I’ve put out a new version (0.98) of the CDK descriptor calculator interface which uses the latest CDK master and also updates the save dialog for the descriptor selections to let the user specify a file name.

Written by Rajarshi Guha

April 3rd, 2010 at 3:19 pm

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From Theory to Practice

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Some time back, John Van Drie and myself had done some work on characterizing structure-activity cliffs, which are molecules that have very similar structures but very different activities. The term originated from Maggiora, who suggested that this was a reason for the failure of many QSAR models. At the same time, such cliffs can represent the most interesting portions of a structure-activity relationship. Our first paper introduced the idea of the Structure Activity Landscape Index (SALI) – a numerical metric to characterize activity cliffs and SAR landscapes, and was followed by a paper describing how one could use SALI to characterize the quality of predictive models. We also put out some software to let others use SALI to analyse their own data.

A few weeks back I heard from Jinhua Zhang at Simulations Plus Inc., that they had implented the SALI methodology in their ADMET Predictor product. He also provided some slides showing how they used SALI to characterize a variety of predictive models for hERG inhibition.

It’s a nice feeling to see our theoretical work being incorporated into a real world product!

Written by Rajarshi Guha

June 21st, 2009 at 9:15 pm

Posted in research,cheminformatics

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The Quest for Universal Descriptors – Not There Yet

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A major component of QSAR modeling is the choice of molecular descriptors that are used in a model. The literature is replete with descriptors and there’s lots of software (commercial and open source) to calculate them. There are many issues related to molecules descriptors, (such as many descriptors being correlated and so on) but I came across a paper by Frank Burden and co-workers describing a “universal descriptor”. What is such a descriptor?

The idea derives from the fact that molecular descriptors usually characterize one specific structural feature. But in many cases, the biological activity of a molecule is a function of multiple structural features. This implies that you need multiple descriptors to capture the entire structure-activity relationship. The goal of a universal descriptor set is that it should be able to characterize a molecular structure in such a way that it (implicitly or explicitly) encodes all the structural features that might be relevant for the molecules activity in multiple, diverse scenarios. In other words, a true universal descriptor set could be used in a variety QSAR models and not require additional descriptors.

One might ask whether this is feasible or not. But when we realize that in many cases biological activity is controlled by shape and electrostatics, it might make sense that a descriptor that characterizes these two features simultaneously should be a good candidate. Burden et al describe “charge fingerprints” which are claimed to be a step towards such a universal descriptor set.

These descriptors are essentially binned counts of partial charges on specific atoms. The method considers 7 atoms (H, C, N, O, P, S, Si) and for each atom declares 3 bins. Then for a given molecule, one simply bins the partial charges on the atoms. This results in a 18-element descriptor vector which can then be used in QSAR modeling. This is a very simple descriptor to implement (the authors implementation is commercially available, as far as I can see). They test it out on several large and diverse datasets and also compare these descriptors to atom count descriptors and BCUT‘s.

The results indicate that while similar in performance to things like BCUT’s, in the end combinations of these charge fingerprints with other descriptors perform best. OK, so that seems to preclude the charge fingerprints being universal in nature. The fact that the number of bins is an empirical choice based on the datasets they employed also seems like a factor that prevents the from being universal descriptors. And, shape isn’t considered. Given this point, it would have been interesting to see how these descriptors comapred to CPSA‘s. So while simple, interpretable and useful, it’s not clear why these would be considered universal.

Written by Rajarshi Guha

February 14th, 2009 at 1:09 am

Posted in Literature

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ONS Solubility Predictions

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Using the model deployment and prediction service, I put up the two linear regression models I had built so far (described in more detail here) While REST is nice, a simple web page that allows you to paste a set of SMILES and get back predictions is handy. So I whipped together a simple interface to the prediction service, allowing one to select a model, view the author-generated description and a get a nice (sortable!) table of predicted values. View it here. As noted in my previous post it’s not going to be very fast, but hopefully that will change in the future.

Written by Rajarshi Guha

January 14th, 2009 at 9:31 pm

Posted in software

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