Drug Design on the Open Web

A few months ago I started working with Mesa Analytics and Computing as a consultant on an SBIR project aiming to provide new tools for drug design. Although the business model component is confidential, a large part of the project involves the use and creation of freely available online tools for educational or other purposes.

This is a great example of a for-profit company aiming to provide significant value in the form of free services for the chemistry and biology communities. ChemSpider is another example.

What we would like to do is provide an intuitive interface for someone to perform some QSAR and docking work.

Mitch Chapman has provided a detailed description of a test dataset we'll use for the QSAR example. The advantage of using this source is that Rajarshi Guha has already created a publicly available service that we can use for performance comparison.

We are updating a "working scenario" to think about how this could all work and identify which pieces are missing. Hopefully we can put together a prototype for Phase I and find the right partners to get something robust constructed during Phase II.

This is all taking place on the UsefulChem wiki and we welcome contributions and suggestions from everyone.

Open Source Science Expands with Tan

A few months ago I posted a request for a docking collaborator to help us understand and reproduce our docking results with our targeted anti-malarial compounds. I've been contacted by a few people and I'll report on every one of those collaborations when it is possible.

Last week, Tan Tsu Soo from the Bioinformatics Group at Nanyang Polytechnic in Singapore informed me that he worked things out with his Director and was now in a position to collaborate with us openly. He has been busy docking uncyclized Ugi products and diketopiperazines using FlexX to compare with the results than Sean has obtained in D-EXP005.

He has not obtained identical results, partly because his search is not restricted to the same binding site that Sean used with THINK.

But the good news is that Tan also has managed to dock a good number of our molecules, including Ugi products that we have made and can start testing. He uploaded some of his results using Jmol to demonstrate the docking. Stay tuned for more data on the wiki.

The deprotected Ugi products (R and S) that Alicia prepared in EXP062 are shown below to dock in a similar fairly shallow location. (DRuncycltBu and DSuncycltBu from D-EXP005) Others, like the catechol derivative BRuncycltBu bind deep into the pocket. Check them out on Jmol.