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25th August 2014 @ 21:41

Attached is the guide for how to obtain MMV numbers for OSM compounds (used prior to shipping to Syngene for potency evaluation). Note this requires a user account from MMV.

Attached Files
1st February 2014 @ 04:21

Molecules developed as part of OSM are given unique IDs. These are supplemental to any synonyms, either local lab book numbers or numbers given by other organisations such as ChEMBL and MMV. The numbering system is:

OSM-X-Y

where X = the first letter of the city in which the compound was made (S for Sydney, E for Edinburgh etc) and Y = a number assigned, incrementally.

Originally OSM numbers were assigned only to molecules that had been biologically evaluated. However, in some cases it is useful to collate all the synthetic data together for synthetic intermediates or for those compounds that are of predicted value to the project that have not yet been synthesised. So all compounds now receive OSM numbers. See GHI 172 for more on this.

The instructions below are for maintaining the OSM compound list and should be followed by anyone making a compound new to the project, or those making sure that their ELN entries are incorporated properly into the list.

1 - Does Your Compound Need a New OSM Number?

The first step is to check whether your molecule has been made before in OSM. One option is a visual inspection of the Master List - either the structure-based page or the strings-based page - if a molecule is not there then it has no OSM number. To be sure, though, it is best to search the OSM lab notebooks using strings like SMILES, InChI and InChiKey. To do this, draw your molecule in ChemDraw (Use Wiley settings) or some other program and copy the string.

Generating SMILES

Paste it into the search box, make sure you're searching across all blogs and hit "search". There will be too many results, so click the "Use simple text search" button and search again.

Searching for whether OSM number needed

From the results, it should be clear if that molecule has been made before and also whether it has received an OSM number. 

If you are in any doubt, contact a member of the OSM team - we must not have two codes applying to the same compound or vice versa. Each unique molecule needs one OSM code. 

2 - The compound already has an OSM number. Go to step 4.

3 - The compound does not have an OSM number.

a) Underneath your structure drawing of the molecule add the caption "OSM-X-Y" (Arial font) as appropriate. Save the .cdx file and save the file as a .png image. You can save these files locally on your computer. If you have access to the OSM Shared Dropbox (Openchem->OSM Compounds) folder, save them there.

b) Log in to Labtrove as osdd.malaria. This means logging out of whatever Google account you are in and logging back in as osdd.malaria, then logging in to Labtrove. If you need the osdd.malaria password, contact one of the OSM team. It is crucial we use this account so that others can edit the entry later with this shared password.

c) Go to the "Experimental Procedures" ELN and click "New Post"

d) Give the post the title "Preparation of OSM-X-Y"

Naming the Post

e) With the cursor in the main window, click on the "upload data" button at the bottom of the page, and upload both the .cdx and .png files to the page. Close the little upload data window.

Adding Data

When the .png file is uploaded click on its thumbnail. In the window that pops up, right-click on the "PNG" link and copy the link location. Close the pop-up window containing the structure.

Acquiring Picture Link

f) Back in the main post window click on "insert picture" and in the window that pops up, in the Image URL field, paste your link for the .png file. In the Image Description field, type "OSM-X-Y" as appropriate.

Inserting the Image Name

In the Appearance tab make the picture 200 pixels wide, then click Insert and your molecule should appear in the window, and with a reasonable size.

Setting the Image Size

g) It is a good idea to publish your entry at this point. This saves it and solves a problem you will have later on if you do not do so. Once it is published, click "edit" to get back into the post.

h) On the line below the picture, add the heading "Original Sources" in bold. Then on the following lines you need to add links to the ELN entries where this molecule has been made or where an attempt has been made to make it. To do this click the "Insert link to blog post" button.

Insert Link Button

In the pop-up window, from the drop-down menu, select the lab notebook where the entry is that you want to link to. Navigate to the entry using the month/year menu on the right, locate your experiment and click it once.

Selecting the ELN Entry

This will insert the link to that post (if the link appears in bold, un-bold it). Importantly, this also inserts a back-link from that entry to the page you're working on. 

i) Repeat for any more links you would like to insert. Once the links are in place, add the next section title in bold, which is "Biological Data" and again add in any links (not bolded) to ELN entries containing such data. There may be none, in which case write "N/A"

j) Give the final section the title "Synonyms" in bold. On the first line after that insert any local lab book codes used for these molecules - i.e. the codes that use the initials of the researchers making the molecule. Just use the initials and the first number without a hyphen.

Adding Headings

On the second line insert any other codes the molecule may have from other databases. On the third line, insert the SMILEs, on the fourth insert the InChI, on the fifth insert the InChiKey and on the sixth insert the chemical name. All of these strings can be copied and pasted from Chemdraw etc.

k) Select the Section "Experimental" from the drop down menu.

l) In Metadata type Osm and in the value field type "OSM-X-Z To OSM-X-Z+9" where Z is chosen so that your compound's number (Y) is between Z and Z+9. Z will be something like 21 or 41 or 81 etc.

m) If a Reason for Edit is needed, then supply one, then hit publish. This will take you to your published page. Congratulations!

Adding Strings

4 - Adding the Compound to the Master List

a) Open the page for the compound you want to add to the master list, or one that you have just added to the Experimental Procedures. In a separate tab go to the Master List and click "edit post" at the bottom of the page. If this option is not available, you are not logged in as osdd.malaria and need to be.

b) Go to the end of the Master List page. Place the cursor at the end of the page, or where you want the picture to appear - the compounds need to be sequential. Go back to your compound's page and click the thumbnail of the .png file, copying the link in the pop-up window as described above. Go back to the Master List and add the picture as described above using the link you just copied. It needs to appear similar to the other pictures, and this will vary depending on the drawing. Usually 80-130 px wide will achieve this. Remember to give the picture its OSM name in the Image Description field.

d) Once the picture is added to the window, click it once and click the "insert link" button, then paste in the URL of the page that describes the compound. Select "Open in New Window" in the Target field and click "Insert". This inserts a link so that someone can click on the picture and be taken to the compound page.

e) Keep other things as they are (Section is Compound List, Metadata are blank) and type "Added OSM-X-Y" into the Reason for Edit, then click Publish.

5 - Making Sure of Discoverability

a) Go to any pages that you linked to in the synthesis page for your compound.

b) Submit a comment that says "OSM-X-Y". This ensures that the pages will be found upon a text search. 

Adding back-link as comment

And you're done!

Linked Posts
Attached Files
20th January 2014 @ 22:28

In this post, how to conduct a search for the commercial availability of a series of similar compounds is exemplified by the search for molecules relevant to series four.

Following Mat Todd’s condensation of the MMV amide spreadsheet into an easy-to-read wiki entry, I have conducted an amine availability search to assist in the selection of five affordable amines to be used in the synthesis of some series four compounds. We will probably choose five new amines and one from the existing library so we can verify the potency results.

Based upon the data already collected for this small library, it seems that high potency requires the inclusion of halogens on the amide substituent and an acyclic amine.

 

Searches were carried out in the following manner:

1. The chemical search engine, eMolecules was used.

2. I began the search with one of the amines from the library, MMV670944, which had promising potency.

MMV670944.PNG

3. This molecule was drawn into eMolecules and an ‘Exact Structure Search’ conducted.

amine_1.png

4. From the results page it was then possible to check the availability and price of the compound by clicking on the ‘Supplier’s ID’ links. Supplier availability and pricing for possibly amines is summerised below.

amine_2.PNG

5. Once the suppliers had been searched, I clicked back to the eMolecules search page. I then conducted a ‘Similiarity Search’ on the same amine. The ‘Similarity Search’ tool proved more useful than the ‘Substructure Search’ function.

amine_3.PNG

6. This yielded a results page showing the suppliers of similar molecules which appear in order of decreasing similarity.

amine_4.PNG

7. Following this, ‘Similarity Searches’ for the following high-potency amides, was conducted.

Amines used for similarity search.png

8. From the resulting searches, amines of interest were selected based on the following criteria.

The amines were:

- not prohibitively expensive

- halogenated

- acyclic (however, in the MMV library there was only one example of a cyclic amide which was also halogenated, so this combination could require further attention)

              

Prices of selected amines from the MMV library:

From MMV library ACS.png


Prices of possible new amines:

Possible amines to try ACS.png
Linked Posts
Attached Files
20th January 2014 @ 11:23

There are excellent how-to guides for using the lab notebook and Github.

There are a few extra general guidelines common to both that need to be borne in mind. These are summarized below, and were originally described here and here. Some points are also mentioned in this guide to making the perfect chemistry ELN entry.

1) Context. A lab book post or a GitHub Issue must have some context, to be clear to an outsider or someone who arrives at the project at that point. For an experiment there should be a reason given for the experiment somewhere near the start, ideally with a link to another experiment or to the literature. For a good example see here. For a Github Issue there needs to be some link out to the reason for a particular issue having arisen and why it needs to be solved. For a good example see here.

2) Completion. If an experiment has been completed, a sentence to this effect (along with the conclusion derived from the experiment) needs to be placed near the beginning of the entry. For Github issues, Issues should be closed, ideally with a comment as to why the Issue is being closed, or perhaps with a link to a more recent Issue that was opened that supersedes the existing issue and makes it redundant.

3) All data. Remember that an ELN entry needs to include all data relevant to an experiment. Raw and processed data. Everything should be present that allows us to write up the compound's synthesis for publication.

4) Citations. ELN entries are the bedrock of the project. If something is being discussed on Github, or elsewhere, about some aspect of the lab work, include links to the ELN to justify statements. e.g. rather than saying "Reaction X appears to be working" instead say "Reaction X appears to be working based on the NMR spectrum [here]" Also within Github, if there are Issues relevant to other issues, simply pasting in the URL for one issue will create a link between them automatically, which can be very useful.

5) Schemes - all ELN entries should have schemes. Github entries mentioning molecules should have pictures - very easy to drag and drop.

6) Strings - Inchis need to be added to ELN entries for molecules that have been synthesized, whether they are the product of a reaction or they have been employed as reagents. Smiles appear to be less effective.

7) Tags in Github. To allow OSM to maintain active collections of activity (e.g. all molecules being made, or all activity on a particular series) we must used Github tags. When creating or commenting on an issue, please consider whether the right tags are being used.

8) When making a molecule. Create a Github Issue for the molecule. Tag it with "Being Synthesised". Provide an approximate timeline for completion of the synthesis, either using Github itself or by writing in a deadline to the Issue. Close the Issue when the molecule has been made.

 

Though these are more things to remember, they will make the ELN and Github much better resources for the project.

This post authored by Mat Todd

10th January 2014 @ 05:36

Welcome to the OSM Team, we're delighted that you've joined the project. This aim of this blog is to provide links to all the relevant information you need to get you started. This post can be used at any institution although there will of course be different guidelines for practical work and analysis at different universities/research institutes and your supervisor will tell you everything that you need to know.

So, first up here is the OSM landing page: www.opensourcemalaria.org. This is the project's porthole and where you will find links to all of the online tools for the project:

The Wiki

First of all, head over the project wiki to find out about the story so far for the OSM project and also the current progress on different compound series. You can sign up for a wiki account here (pending Mat Todd's approval) and then you will be able to edit and contribute to these important pages.

The ELN

The most important tool for the project and most especially for us experimentalists is the electronic labnotebook (ELN - http://malaria.ourexperiment.org). This is the place where the team writes up ALL experiments and posts ALL data as soon as is physically possible. The ELN is one of the features of the OSM project that sets us apart from other drug discovery teams. All of our data and experiments can be viewed by ANYONE who has access to the internet. It is therefore really important that the ELN is maintained to the highest of standards so that anyone could follow the procedures or use the data. One important feature of the ELN is something called revision history. This means that although posts can be edited, a record is kept each time changes are made to a post. This is an essential feature for a scientific project as a lab notebook is a legal document and its is important that noone can change data or modify results. 

But what if I make an error or mistake? Don't panic, that's fine we all make mistakes! Of course its good to check over work for calculation or typographical errors before publishing but its fine to edit any errors. Each time you make an edit, a short comment is required to detail the reason that changes have been made. If something goes wrong with your experiment (even the best chemists occasionally drop a flask!), again don't worry just make a note of what happened on your lab notebook. Remember, some of the most important scientific discoveries have been the result of serendipity so it's important to record what you did accurately and what happened so that you (or any other chemist) can repeat the experiment again.

OK, so how do I complete a 'perfect' entry in the ELN?

Glad you asked:

1) First of all you need to sign up following this guide.

2) Follow this template for excellent results.

A word about Hazard and Risk Assessment (HIRAC)

The HIRAC is an essential part of each experiment and should be completed BEFORE you even remove any chemicals from the cupboard. The template is found here and a new HIRAC should be completed for every new reaction that you perform or if you scale up a reaction that has already been performed. Each HIRAC MUST be signed by either Alice or Mat prior to starting your reaction. More details can be found in the school safety handbook (also found here) and you should read this before conducting any experimental work.

GitHub

The main feed found on the project landing page is directly updated from OSM's GitHub repostitory. GitHub is the organisational tool for the project and is where the 'to do list' is hosted and edited. GitHub allows anyone (in- or outside of the project) to see what's going on and what needs to be done and hopefully prevents dupliation. To sign up to Github follow this guide and then you can join in discussions or update issues once completed. 

Twitter, G+ and Facebook 

The above social media sites are used to promote and publicise the project but also as important platforms for discussion. Many great contributions are received as comments on these sites so it would be great if you signed up for accounts (particularly for Twitter and G+).

Mugshots

All members of the team have a picture on the 'meet the team' part of the landing page. To be added to this hall of fame please sign up for a gravatar account and email opensourcemalaria@gmail.com from the address you used to sign up to gravatar. Alternatively, you can send us a picture but gravatar is preferable.

Specific Links

Many useful links for USyd chemists can be found here. Other institutions that would like to link from this page please comment below and the team will add the links.

Hopefully this page will help you to get started as part of the OSM team, it can seem daunting to sign up for so many accounts but each of these tools are helping us to run the project as efficiently and 'open-ly' as possible. As always, if you have any comments or ideas such as how to improve this blog or about the project please let the team know. Comment below or on G+, Twitter or facebook

Welcome onboard and good luck with your reactions.


Cheers,

Team OSM