Dana Vanderwall on Cheminformatics at Drexel

Dana Vanderwall, Associate Director of Cheminformatics at Bristol-Myers Squibb, presented for my last Chemical Information Retrieval class on December 2, 2010.

The first part covered "Cheminformatics & The evolving relationship between data in the public domain & pharma" and included a general discussion of modern drug discovery and the details of a malaria dataset recently released from the pharmaceutical industry to the public.

Vanderwall cheminformatics Drexel Part 1

View more presentations from Jean-Claude Bradley.

The second part described a project based on "Molecular Clinical Safety Intelligence", where tracking side effects from approved drugs can help in the design of new drugs.

Dana Vanderwall cheminformatics Drexel Part 2

View more presentations from Jean-Claude Bradley.

It was a very nice way to close out the course, showing very practical applications of the concepts we covered over the term. The recording is available below.

Drexel Chemistry Mini-Symposium on Bradley Lab

Every year the chemistry department at Drexel gives faculty the opportunity to present their research to incoming students in 10 minutes slots. On September 30, 2010 I presented on "Open Notebook Science for Malaria Drug Discovery and Solubility Modeling". I think such a short format is good for keeping student attention. Recording it also provides a handy link to use for other purposes. Most people just don't have time for 30-60 minute presentations.

Bradley Drexel MiniSymp 2010

View more presentations from Jean-Claude Bradley.

The Fall 2008 ACS meeting ends

It is always nice for a major conference to happen on home turf. Last week the American Chemical Society held its fall meeting in Philadelphia.

I finally got to meet my Second Life collaborator Andrew Lang during our first talk on Monday August 18, 2008. We presented on what is now possible to do for chemistry in Second Life. There are now several easy to use tools for chemistry and molecular biology. For example, Andy has created a tool to display protein surfaces using a lightweight sculpted prim from a PDB file. Take a look at the slides from the presentation for a quick overview.


I gave another talk on Monday about Second Life and Social Media: Networking Goldmine or Time Sink? It was a nice opportunity for me to talk about major success stories (Bora Zivkovic, Beth Ritter-Guth and Deepak Singh) as well as specific examples from my own experience. Sandy Adam from Sigma-Aldrich and Andy Lang contributed their own stories at the end. The take home message was that if you treat these platforms as a means of participating with your scientific community you're likely to get out of it more than you put in.

On Wednesday I spoke about Open Notebook Science and the value of raw data in drug discovery. The timing was perfect, since I had just finished analyzing the correlation of our docking predictions with biological assays against falcipain-2 and Plasmodium falciparum. (data here)

Scribd as a Repository for Proposals and Science Docs

Since Nature Precedings has tightened its policies and no longer accepts proposals, I have been looking for some alternative PDF repositories.

I think it is very important to have a convenient way to cite these documents on platforms with third-party timestamps and all the bells and whistles of web2.0 - ratings, comments, easy sharing tools, etc. Open Science is not just about what we are doing but also where we're headed.

Scribd seems to be a good solution. I've posted my last proposal to the Gates foundation there, in addition to the SCIEnCE site.

Gates Submission on ONS, crowdsourcing and malaria

On Friday I submitted a proposal to the Gates Foundation's Grand Challenges Explorations:

Creative, unorthodox thinking is essential to overcoming the most persistent challenges in global health. The first vaccines were developed over 200 years ago because revolutionary thinkers dared to try an entirely new approach to preventing disease.

The power of innovation is at work in countless other fields, from space travel to the Internet: now is the time to harness that power to save lives and improve the health of millions of people in the developing world.

Grand Challenges Explorations will foster innovation in global health research and expand the pipeline of ideas that merit further exploration. The initiative will use an agile, accelerated grant-making process with short two-page applications and no preliminary data required. Initial grants will be awarded multiple times per year at approximately $100,000 each. Additional funding of $1 million or more will be available for projects that show promise.

There is a 2 page limit so the proposal was painted in very broad strokes. Since Nature Precedings doesn't take proposals anymore, I just uploaded it to Noam Harel's SCIEnCE wiki. The core concept is leveraging crowdsourcing and Open Notebook Science to develop new anti-malarial agents. It is similar to the last NSF proposal I submitted, except that the purpose is squarely on drug development, which is not allowed for NSF funding.

I also broke it down into short sections and contributed it to the Thoughtmesh project just to see how that works.

Cell Article on Open Drug Discovery

Seema Singh wrote a review "India Takes an Open Source Approach to Drug Discovery" which just appeared in Cell: Volume 133, Issue 2, 18 April 2008, Pages 201-203. (The doi doesn't work yet but try this link in the meantime). You'll need a subscription to view it, an increasingly familiar irony of much of the Open Science discussion these days.

UsefulChem and our collaborators got a nice mention:

A related initiative is UsefulChem (http://usefulchem.wikispaces.com/), set up by Drexel University chemist Jean-Claude Bradley. Bradley has pioneered Open Notebook Science in which lab notebooks and raw research data are posted on the web for anyone to see and respond to (http://usefulchem.wikispaces.com/All+Reactions). As for success, Bradley says, “Probably the best example of a positive outcome from UsefulChem is finding two compounds that are somewhat active against malaria [in vitro],” blocking the activity of falcipain-2, a Plasmodium falciparum cysteine protease. “This demonstrates that a team of researchers can work together in the open—Rajarshi Guha from Indiana University did the docking calculations, my group at Drexel did the syntheses and Phil Rosenthal's group at UCSF did the testing.”

Scholar2Scholar Tomorrow

The Scholar2Scholar conference is upon us. Jay Bhatt and Anita Chiodo did an amazing job with organizing this from the start. I'll be giving the introductory talk on "Enhancing Scientific Communication through Open Notebook Science". Here are the slides - I'm starting with an introduction to Web2.0 using FriendFeed as an example.

| View | Upload your own

date: April 16, 2008 8:30-1:30
location: Drexel University Bossone Lobby

Join us to discuss how Web2.0 is changing scholarship. Dr. Jean-Claude Bradley will give a presentation, followed by a panel discussion featuring: Andre Brown, Nicole Engard, James Mitchell, Banu Onaral, Beth Ritter-Guth, and Scott Warnock. Small round-table discussions will follow. An optional Dutch-treat lunch concludes the day.

We're Gonna Ugi All Night!

Thus begins the CHEM254 lab manual for the week of April 7, 2008 at Dominican University:

“Ugi to the left, Ugi to the right. This is so fun, we’re gonna Ugi all night.”

As I discussed a few days ago, Brent has followed through in a big way in incorporating the UsefulChem project into his teaching lab:

This experiment represents the beginning of collaboration with the UsefulChem Bradley open notebook science group of graduate and undergraduate research at Drexel University. The goal of the UsefulChem project is to use the Ugi 4 component reaction to synthesize possible anti-malarial compounds. Open notebook science allows immediate dissemination of experimental results that invites advice and suggestions as well as complementary experiments that enhance and advance the project. We are going to reproduce some of the Drexel results as well as perform two complementary reactions that have not been done at Drexel.

The procedure is derived from our lab notebook with one interesting vortexing modification :)

Part I.
Add 0.33 g of your aldehyde to 8 mL methanol in a 20 mL scintillation vial.
Screw on a Teflon (green) cap on the vial. Vortex to mix and dissolve the aldehyde.
Add 1 mL of methylamine solution to the vial.
Vortex to mix. Sing the “Ugi song” while vortexing.
Obtain 0.34 g of the carboxylic acid. Add the carboxylic acid to the vial.
Vortex to mix.
Obtain 0.39 g of tosylmethylisocyanide. Add the tosylmethylisocyanide to the vial.
Vortex to mix.
Take a photo of your reaction mixture.
Label the vial and let the reaction mixture sit in the sealed vial.

By taking pictures his students can directly compare the progress of the reaction with our group. The questions for this lab are also excellent and may result in some useful ideas for my students to ponder (this may end up being a realistic way to foster chemistry crowdsourcing):

What could you do to isolate your product if after 7 days if there are no spontaneously formed crystals?

Refer to UsefulChem Experiment 171 . Which reaction most closely corresponds to our experiment? What were the results?

Consider the IR spectrum may reveal that there is unreacted isocyanide in your product mixture. Where does the isonitrile group appear in an IR spectrum? (Refer to appendix 2B in your textbook.)

Consider the possible 1H spectrum of your Ugi product. How many aromatic Hydrogens are there? How many methyl groups are there? Where would you expect to observe the methyl groups?

Consider the possible 13C spectrum of your Ugi product. How many aromatic Carbons are there? How many carbonyl carbons are there? How many methyl carbons are there? Where would you expect to observe the methyl carbons?

If you were given four different compounds for each type of Ugi reactant (16 compounds in all), how many different Ugi products could you attempt to make?

Safety Question: What is the safest way to transfer 1 mL of 2.0 M methamine in methanol from the stock bottle to your reaction vial? Give a reasonable explanation of your choice.

I also really like that he is exposing his students to some handy cheminformatics tools:

Look up “tosylmethyl isocyanide” in chemspider. What is the InChI code? What is an InChI code?

Since Brent and I started the discussion we have a few more precipitates involving the non-stinky tosylmethylisocyanide that may be suitable for his lab. Khalid has been doing some tedious but very necessary data checking and recording and the updated results are available on the Master Table of Ugi reactions.

There are currently 65 reactions, with 20 giving precipitates - and we are now including reactions where the starting materials fail to dissolve. Not all the precipitates have been characterized but they will be over time. In fact the Ugi product that Brent is trying to make in his lab for next week has not yet been fully characterized - all those phenolic groups seem to give rise to solubility issues in CDCl3.

That is a risk associated with using Open Notebook Science for a teaching lab. But it is also one that could pay off because his students could be contributing valuable results to an ongoing research project focussed on making anti-malarial compounds.

Expanding the UsefulChem Collaboration to Teaching Labs

A few weeks ago I received a very interesting email from Brent Friesen at Dominican University. He mused:

I am trying to put together a bridge between the type of opensource research you are instigating and the traditional Sophomore Organic Chemistry lab. There are over 4,000 college and universities in the United States - all of them teach Sophomore Organic Chemistry lab. How can we harness this resource? .....

SOC labs must fulfill 4 criteria:
1) inexpensive reagents and equipment
2) fit into the time constraints of 1 3-hour period per week.
3) Must be a robust reaction with fairly stable products. It doesn’t have to be “foolproof” but that helps.
4) Compatible with equipment, glassware, procedures that student know how to use and do.

Bottom Line: I am definitely interested in developing collaborative projects, especially if they can be performed as part of a Sophomore Organic Chemistry laboratory curriculum.

This is extremely encouraging news for open scientific collaborations and I am very impressed with Brent's initiative! It certainly is more work for him compared to maintaining the status quo.

Kevin Owens and I have discussed this possibility for some time now and he is willing to contribute by carrying out mass spectrometry if required.

Brent and I further discussed the applicability of the Ugi reaction that we perform in my lab because of its simplicity - 4 components are mixed together in methanol at room temperature and a Ugi product often precipitates within days, requiring only filtering to isolate. (see EXP150 for a good example)

However, one major limitation of the Ugi reaction for a teaching lab is the terrible stench of most isonitriles, one of the four key components. One way around this is to use isonitriles that don't stink, such as TOSMIC.

So as a starting point, we would like to start with a Ugi reaction which involves TOSMIC and has lead to a precipitate in our lab. There is only one example so far: 171H.



According to the lab notebook, all starting materials dissolved easily and a precipitate appeared after 2 days. The precipitate has not yet been isolated and characterized. Hopefully it will prove to be pure Ugi product, as other similar Ugi reactions have done.

It turns out that many of the top ranking compounds from Rajarshi's falcipain-2 docking run (V2) contain TOSMIC as the isonitrile. Phil Rosenthal at UCSF is still up for testing compounds for anti-malarial activity. Wouldn't it be a testament to the power of open collaborative science if a decent anti-malarial lead was uncovered through the routine teaching of undergraduate organic chemistry labs?

At the very least I'll bet it would be rewarding for the students involved.

Brent has placed the orders from Sigma-Aldrich and is moving full steam ahead. He recently wrote to me:

You know, I'm ready to dance and you are the only dance partner who seems to be ready and willing. Let's figure out a way to adapt the Ugi reaction to Sophomore Organic Chemistry laboratory and give it a try!

I would like to plan it for the week of April 7 and the following week...
Does not give us much time, but it can be done.

Keep track of Brent's activities on his blog.

Tags
171H InChIKey XRHVBZVCUGMHPN-UHFFFAOYAR
TOSMIC InChIKey CFOAUYCPAUGDFF-UHFFFAOYAC InChI=1/C9H9NO2S/c1-8-3-5-9(6-4-8)13(11,12)7-10-2/h3-6H,7H2,1H3

Andre Brown's Talk on Science2.0

From Bora Zivkovic's A Blog around the Clock:

Here is a video of SPARC-ACRL Forum '08 on 12 January, 2008 at the Pennyslvania Convention Center in Philadelphia:

The SPARC-ACRL Forum at ALA '08 entitled "Working with the Facebook generation: Engaging students views on access to scholarship." Panelists discuss the merits of student activism, patent reform, blogs as a communication medium for scientists, and students as active members of a discussion about the right to access information for scholarly work. Features Andre Brown, Nelson Pavlosky, Stephanie Wang, and Kimberly Douglas as panelists.

Pay particular attention to Andre Brown and minutes 42-55 as he talks about science blogs and Science 2.0 including
mentions of all the usual suspects (Jean-Claude Bradley, Rosie Redfield, Reed Cartwright, Bill Hooker, Peter Suber and me):

SPARC-ACRL Forum '08 from Matt Agnello on Vimeo.

Andre Brown does a really good job of summarizing the key points of the potential of social software in communicating primary research.

UsefulChem gets a mention around minute 50 and Gus Rosania is used as an example of how blogging about science can facilitate collaboration (minute 52).

We Have Anti-Malarial Activity!

The results are in.

Jiri Gut from the Rosenthal group has run 2 of our Ugi products and they both show inhibition of falcipain-2 (EXP165) and Plasmodium falciparum (EXP166) in the micromolar range.

To put this in context the activities are roughly 2 orders of magnitude lower than the positive control used for the enzyme inhibition and chloroquine for the parasite.

But it is a start. And we have officially closed the Open Science Loop for the malaria project, meaning that we have openly documented the docking results from Rajarshi Guha (D-EXP014), our syntheses (EXP148 EXP150) and testing (EXP165 EXP166) in the Rosenthal group.

We can't tell much about the validity of Rajarshi's docking model from the results of two compounds but as more data come in the situation should become clearer.

However, Jiri did make this interesting observation:

The food vacuole abnormality, which is indicative of cysteine protease inhibition was not observed in the parasites, suggesting other mode of action.

Chemistry Crowdsourcing with Open Notebook Science

I recently submitted a Letter of Intent for the NSF Cyber-Enabled Discovery and Innovation competition. Kevin Owens is a co-PI and will assist with the laboratory automation component. ChemSpider will contribute the database support. The pre-proposal is due in early January 2008 and we'll be writing it openly here. Comments are welcome.

We would ultimately like to enable the chemistry community to directly control the actions of a robot to help us understand some chemistry problems. As we make our way towards this goal, it would be very useful to start with suggestions for protocols to be executed by students we currently have in the group.

We already have a mechanism in UsefulChem to post experimental plans. In order to make the transition to full automation easier, it would be preferable if suggested protocols are even more specific than what we currently have listed. For example, instead of describing a general procedure like EXPLAN005, actually specify all of the compounds, amounts, mixing times, etc. This way the protocol can just be copied and pasted in the Procedure section of a new experiment, executed faithfully and reported in the main experiment list.

The main puzzle to solve is the prediction of which Ugi products will precipitate. A hypothesis might be that a precipitate will always occur from methanol at a certain minimal concentration of a certain reagent. Another approach might be based on the predicted molecular descriptors of the Ugi products. We might also start with as few assumptions as possible and use a genetic algorithm to evolve a solution. We'll be doing some of these but clearly there are more ways to solve this puzzle than we have resources or expertise.

So if anyone is interested in participating at this stage contact me to get access to the wiki and further discuss. Other examples of chemistry crowdsourcing : Chemmunity, The Synaptic Leap, OrgList, Chemists Without Borders and ChemUnPub.

Here is the LOI:

Chemistry Crowdsourcing using Open Notebook Science

The current system of dissemination of scientific data and knowledge is far less efficient than it needs to be to facilitate improved collaborative science, especially considering current publication vehicles and infrastructure. There is a growing movement promoting more Open Science, with the belief that a more transparent scientific process can perform far more effectively. The logical extension of this concept is full transparency - exposing a researcher's complete record of progress to the public in near real time. Not only will such a process enable ongoing data sharing it also provides an opportunity to develop collaborative communities of scientists and, at the conclusion of data acquisition, can enable communal extraction of conclusions when necessary. We have named this approach Open Notebook Science and have demonstrated its implementation and feasibility with the UsefulChem project, started in the summer of 2005, with the aim of synthesizing novel anti-malarial compounds. Our system currently uses free hosted services using general blog and wiki functions to facilitate replication across any scientific domains. These services are not chemically intelligent and are limited to text and graphic based data sharing only. For Open Notebook Chemistry the ability to intelligently manipulate, manage and search chemical structures and associated data is necessary and we have demonstrated proof of concept capabilities by integrating with the ChemSpider service, a free access online database managing chemical structures and focused on developing a structure centric community for chemists. This work will require the development of a chemically intelligent software platform to extend the capabilities of both the blog and the wiki environment for managing Open Notebook Science. The exposure of raw experimental procedures and data in a semantically rich format will enable the participation of both human and autonomous agents in the process of scientific discovery. This phenomenon of spontaneous group intelligence, referred to as "Crowdsourcing", has proven valuable in several contexts. Already, productive collaborations have been forged within the UsefulChem project with groups from Indiana University, Nanyang Technological University, the National Cancer Institute and UC San Francisco.

First Falcipain-2 Targets Shipped

We've reached an important milestone on our CombiUgi project involving the synthesis of falcipain-2 inhibitors. In my last update I described how our focus was more on doing many reactions in parallel and only looking for Ugi products that precipitate in pure form within a few days.

It took little longer than I hoped. In order to do more reactions, we reduced our efforts towards monitoring. One of the assumptions that we made was to trust a bottle's label to accurately describe its contents. That turned out to be incorrect for one of our key aldehydes, as we eventually found out by systematically taking NMRs of the starting materials. Soon after ordering a new bottle of phenanthrene-9-carboxaldehyde we were treated to the growth of beautiful crystals (see EXP150 by Khalid and Emily):

This compound was ranked 155th out of 71,000 Ugi products for docking with falcipain-2 at potential receptor site V1 (see full description by Rajarshi Guha here).

This compound, along with another (EXP148) that crystallized similarly, have been shipped to the Rosenthal group at UCSF for testing against the malarial parasite and hopefully get some falcipain-2 inhibition assay results. That way we'll be able to investigate the validity of our docking model.

I'll be posting updates on this blog but the status of any shipped compounds will be maintained on the isolated compounds table.

If anyone would like to run their own assays please contact us. We would be happy to ship any of these compounds, as long as our collaborators are willing to work under Open Notebook conditions.

The beauty of screening for products that are purified by crystallization is that, if any of these prove to be useful for any application, it should be very simple and cheap to produce several kilograms. This can come in handy for end users with very limited resources.

Chemical Blogspace Tags

InChI=1/C15H10O/c16-10-12-9-11-5-1-2-6-13(11)15-8-4-3-7-14(12)15/h1-10H
Phenanthrene-9-carboxaldehyde

InChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3
tert-butylisocyanide

InChI=1/C4H6O2/c1-2-3-4(5)6/h2-3H,1H3,(H,5,6)/f/h5H
Crotonic Acid

Swarthmore Talk on Open Notebook Science

On Tuesday November 27, 2007 I had the pleasure of speaking at Swarthmore on our UsefulChem project and Open Notebook Science more generally.

Liz Evans and Cheryl Grood from the Swarthmore Sigma Xi Chapter did a wonderful job in rounding up people to have discussions both before and after my talk at dinner. This gave us an opportunity to share teaching experiences with new technologies (blogs, wikis, Second Life, etc.) - something I didn't really get into too deeply during my talk.

The timing was also quite fortunate because I was able to discuss an important new result from our lab (EXP148) obtained just a few days ago. (More on this shortly in a separate blog post).

I had some very thought-provoking conversations with both students and faculty. One of the recurring questions was what format Open Notebook Science would take in various scientific fields. Some disciplines, like mathematics, don't have formal laboratory notebooks like synthetic organic chemistry. But there are still ways of reporting daily progress.

The recording of the talk is now available here.

UsefulChem on CDD

Barry Bunin from Collaborative Drug Discovery (CDD) has just given me word that UsefulChem now has an account on their database free of charge. Their current business model involves charging data contributors so I appreciate the invitation.

Our account can be accessed at http://www.collaborativedrug.com/ (user: usefulchemistry, password: cdd). There is currently a set of compounds from our molecules blog. One of the features that I think will be useful for us is a way to record assay results. This comes in at a good time, since we just received the first results from the National Cancer Institute on the screening of one our compounds against tumor cell lines.

It will be interesting to compare CDD with other services like ChemSpider, as they evolve. One current limitation with CDD is that it is not possible to create links to molecules or assays that are truly public and indexable.

However, they are making some data pseudo-public by providing a public username and password (UsefulChem is not yet part of this beta):

http://demo.collaborativedrug.com/ (login as demo, password cdd)

More on this from their recent press release:

Collaborative Drug Discovery (CDD, Inc) is pleased to announce the introduction of its next generation database technology. Collaborative Drug Discovery's Web-based database enables scientists to collaborate in novel, global efforts to more effectively develop new drug candidates for commercial and humanitarian markets. The technology enables novel community-based research efforts that become more and more useful as additional participants contribute data. Publicly available data sets currently in the system include the FDA orphan and approved drugs and small molecule drug discovery data dating back over half a century. These data sets pertain to a diverse group of neglected diseases, including malaria, tuberculosis, African Sleeping Sickness, Chagas Disease and Leishmania.

CombiUgi: Time for Synthesis

For those who have not been following the progress of the CombiUgi project on our mailing list, here is a brief update.

The basic idea is to generate libraries of compounds that can be made quickly in the lab. The compounds in these virtual libraries are then prioritized according to potential usefulness (anti-malaria, anti-tumor, etc.). The top hits are then synthesized and tested.

We chose the Ugi reaction because it is very simple experimentally - mix four components (an amine, an aldehyde, a carboxylic acid and an isonitrile) in methanol at room temperature. In the creation of the libraries we used only components that were commercially available.

In our first library of 68,000 compounds, although all starting materials were commercially available, one of the main components needed (2-naphthyl isonitrile) for predicted anti-tumor activity was not available to ship for 6 weeks.

Since it is important to keep this science loop as short as possible we reran the library generation with Rajarshi Guha's open web service using only compounds that were next-day shippable. We also used this opportunity to increase the number of compounds in the virtual library to 500,000.

Rajarshi has now provided the docking results of this library with malarial enoyl reductase (PfENR). Here is what the top hit looks like:

So far we have been doing Ugi reactions usually with intensive NMR monitoring of each step. This has been very useful in debugging experimental conditions and reagent choice. Now that we have a better understanding of how to do it, generating many products quickly is more important than close monitoring.

We will take advantage of our observation that most of our Ugi products simply precipitate from solution over the course of a day. Instead of looking into additional purification techniques, we will make this an additional requirement for a compound to be considered a suitable lead. Any reactions that fail to precipitate within a day will be noted and discarded (see protocol). This information could surely be of use to others looking for suitable compound libraries.

As for the testing phase of these potential anti-malarial agents, I have a few very promising leads now and I'll report shortly when I get confirmation of a collaborator.

UsefulChem on Drexel Island

Today, I added a little section for UsefulChem on the northeast section of the Drexel Island in Second Life. There are slides from my presentation at the ACS on Open Notebook Science as well as a pic of one of our Ugi products docking in enoyl reductase. The 3D structure of the molecule is also floating there, ready to be rotated and inspected.

We're now working on getting the docking visualized in full 3D space. Eloise is helping with that now.

Don't be shy - come visit! (slurl)

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.

Marketplace Segment on Open Notebook Science

The NPR interview on Open Science I discussed two weeks ago has aired and is now available.

I think it was very well balanced. The positive aspects of not losing failed experiments was weighed against the difficulties in publishing in some journals and of deriving profit.