February Features

Here's the roundup of our latest features from the month of February.

Find chemicals more easily in our database

We've added the ability to search for multiple structures in our curated database. This feature is especially useful if you've saved one of your collections (or our whole database) for in-house processing and you would like to use our procurement services to easily purchase your results.

Additionally, the Find Chemicals feature is now available without first signing in, if you would just like to quickly check for a molecule.

Download everything from one place

If for whatever reason you would rather use your in-house screening tools, you can still get all the benefits of our curated database. The contents of our complete database are available in a single SDF file from a memorable address. You can freely download it, work with it locally and come back to our Find (Multiple) Chemicals page to buy your best hits.

Creating collections by drawing

We mentioned this feature in our previous post but it is worth repeating here: we've expanded the New Collection button with the ability to directly upload your SDF file or start off the created collection by drawing in a molecule first. 

New tutorial videos

Do you want to know more about how our Find Chemicals, ChemAxon properties, 1-Click Scaffold Hop, 1-Click Docking and FTrees features work? We've prepared short, 5-10 minute videos that walk you through the whole process.

Revised quote form

We've moved around some fields, now ask for only the necessary information, but also added a field where you can enter a promo code. Incidentally, we are running a promotion until the 31st of March: if you enter mcule1storder when requesting a quote, you will get 15% off from your order — large or small — on mcule.com!

Easier 'search on this collection' action

On every collection you can now find a 'Search' button that sets up a new Workflow with your collection set as the input. This makes it easy, for example, to continue refining the results of a previous workflow.

Small tidbits

• Made possible to download docking poses just like in 1-click docking since the download pdb option in the glmol viewer basically only works in chrome
• Can't use a 'running' collection as input
• We now send email about quote being processed (for registered users)
• When there are so many collections that it requires scrolling when adding a molecule to a collection, if a new collection is created, the list now scrolls to the bottom.

Growing Beyond 1-Click Docking

In this post, we'll show you how to go just one small step beyond our 1-Click Docking tool, and how this is actually a giant leap for your productivity.

If you're using our 1-Click Docking feature, you already know how simple and quick it is to get a first insight into about a ligand-target interaction and affinity: just draw in a ligand, select a target and push a button: within 60 seconds you are presented with your results. But what happens if you want to do a bit more than that, refine some parameters, dock more than one ligand in one go, customize the binding center or save your results permanently? You can do all this and more, although it might take two, or even three clicks (but not much more!), after a free signup.

The Workflow Builder follows the same flow as the 1-Click tools: there's an input, we do some processing and save it to an output. By default, the input is set to the Purchasable compounds collection, containing more than 4 million unique, purchasable compounds that have gone through our rigorous registration system, but you can also use your own collection of molecules, either by uploading an SDF file, or by drawing in a molecule, just as you did with the 1-Click tools:

The first benefit of using Workflow Builder is that since we're using a Collection as input, we can dock more than a single molecule after one another into the same target automatically.

The meat of a  "Two-Click" docking workflow contains a single Docking (Vina) filter, which is unsurprisingly similar to the 1-Click version, but with a few more parameters you can set:

As opposed to 1-Click Docking, where your results are ephemeral, a Workflow's results are themselves saved to a Collection, whose name we can specify:

And after pushing the Run button, we get our results, just as with 1-Click Docking. The difference is that these results are not only stored for your future reference, but can also be used as an input for your next workflow.

As a free registered user of mcule.com, you can dock 500 molecules each month for free. If you get the taste for docking, you can sign up for a 100k package.

Introducing our new design

You might have noticed that mcule started looking a bit different (frankly, much better) in the last few days. To reflect the fact that we are no longer in beta, we've decided that our design needed to grow up as well. There are still some pieces that need to fall in place, and of course, we are continuously improving mcule, but we are excited to introduce the new site and show you some of the biggest improvements we've made.

The new Dashboard

When you are logged in, the first page you'll see from now on is the Dashboard. From here you'll be able to quickly access all areas of mcule: the 1-Click Applications, your recent Collections and search results as well as predefined Workflow templates you can use as jumping off points.

Restructured navigation

We've given more descriptive names to our Search and Screen features. From now on, you will be able to make simple Exact, Similarity and Substructure searches on the Find Chemicals page. The Workflow Builder is the new, more descriptive name for what was previously somewhat opaquely called Screen. We've moved their links around on the top navigation bar as well.

Pre-defined Workflows

We've added three workflow templates that are accessible from the Dashboard to help you get started using the Workflow Builder. Each template is usable by itself, but really, they are meant to show you how you can use our filters to achieve various tasks. Feel free to experiment!

Workflows now flow

We’ve split the form we’ve used previously into two, so it’s easier to see what the input and output is in the Workflow Builder. Sounds like a minor change, but we think it greatly clarifies how to better use this feature. For example, did you know that you can use any previous workflow's result as the input for the next one? T

Simplified input

If you just want to paste an InChI or a SMILES, why waste your time fiddling with the sketcher? Or, if you’d like to draw in your molecule, why would you need any other fields? Input is now quicker and easier, not to mention less confusing.

All the small things

Fixing the bug that's been bothering us for days or adding a small button to a page in just the right place is unlikely to make the headlines, but nevertheless they are important. Who knows, maybe you bumped into one of them and you'll be glad to know that it's fixed, or that it's there. We've collected some of the smaller but no less important changes we've made:

• You can upload molecules directly when creating a new collection
• When viewing a docking pose, the view is rotated around the docked ligand
• When viewing a docking pose, the docking target's name brings you directly to the target's index page
• Fixed issues with unnecessarily added or missing bonds in GLmol
• In the Docking (Vina) filter, you can now specify a binding center by clicking on an atom in the viewer
• Uploading a .sdf.gz no longer gives an error
• You are now notified if you are over your limits before you submit a new screen job
• You are now warned if you add the same property twice in the property filter
• and various other fixes and improvements on the backend

1-Click Docking

"Docking has never been easier!"

This is the phrase we use when talking about our latest feature: 1-Click Docking. It might sound like a marketing phrase, but it's true. At least I'm not aware of any simpler solution for molecular docking. Here are my reasons:

1. It is online
Desktop applications can't be simpler by definition - think about downloading, installing, running software. 1-Click Docking is online, you go to this URL and it is immediately there, ready to use.

2. Javascript Editor
You don't need to wait for Java-based molecule sketchers to load, again you go to 1-Click Docking and ChemWriter, the Javascript editor is immediately there, so you can start drawing your ligand.

3. Select a target
We have integrated scPDB, which allows you to select a target from 10,000 target structures. No need to download, upload, select binding site, etc. (Note: upload is also possible, but requires registration)

The idea of 1-Click Docking came from our user feedback, which can be summarized with a single word: simplify! They told us that functionalities accessible under the "Screen" tab at mcule.com are really useful, but only for those who know how to use them. So to eliminate the barrier, we decided to introduce 1-Click Applications, which are extremely easy to use.

With 1-Click Docking you only need to draw a ligand, select a target and click on Dock. Then you start browsing the results. Ideal for a first insight about ligand-target interactions and affinity. In some cases that's enough to test your idea. If you need more, take the next step and learn how to use the Docking (Vina) workflow step.

Have a nice docking!

About this StartupSauna thing...

Mcule has been selected as one of the most promising startups from Northern Europe, Baltics and Russia, as a result we are now in StartupSauna in Helsinki, Finland for a one month training. We have been through a lot, improved our presentation skills and got very useful feedback about our business model, products, etc. Here is a nice video showing a little bit of the essence of the whole thing:

Two more weeks are still to go, and we are very excited about it. Of course we keep working on mcule (we are right after a very reasonable release), but this period is very important for us in terms of how we should build our business, marketing strategies, etc. So this is a great atmosphere here in Helsinki that accelerates the transformation of "ideas" into viable companies. It would be great to have more of such incubators for startup companies.

Major release

Subscription packages, user molecule upload, docking visualization and more!

It has been a while since the last major mcule release, but now it is time for a big announcement! We are really proud of the outcome, so here are the new features:

1. Subscription packages

OK, here is something brand new in this field: you can now hire a single tool for a single project! This means that in contrast to the typical annual licensing schemes of modelling software companies we offer our packages for 1, 3, 6, and 12 month periods. You don't have the budget for maintaining an annual license for a tool? No problem, subscribe only when you really need it. Subscribing is super-easy: can be done in 1 minute!

We have signed partnership agreements with BioSolveIT and ChemAxon about distributing their products at mcule.com. As a result you can now subscribe for drug discovery tools of these software companies here. Besides, we are also introducing two mcule packages, but let's go step by step.

FTrees Visual Similarities is a great tool for scaffold hopping. It not only identifies diverse novel active scaffolds but it also tells why the query and target molecules are similar.

Physicochemical properties calculated by the popular Calculator plugins of ChemAxon are widely used and are known to give excellent correlation with experimental data. More than 100 precalculated ChemAxon properties for the whole mcule database are available in the "Properties Access" package option (Academic users: it's free, so go to the Pricing page, apply, and we will switch it on for you). To calculate ChemAxon properties with all possible settings, you should subscribe for the "Properties Access and Calculator" package option.

First mcule package is: Database Access. It gives you access to two things: (i) Product filter, and (ii) exporting chemical supplier data. The Product filter is very useful to filter by supplier names, catalogs, stock availability, price, delivery time, etc. For example it can help to filter out unreliable suppliers and virtual compounds.

Second mcule package: Docking (Vina). The 100k package option allows you to dock up to 100,000 molecules each month. We are planning to introduce a 1M package later on.

For more information about the subscription packages and package options check out our Pricing page. To learn more about the individual drug discovery tools available at mcule.com, check the mcule documentation.

2. User molecule upload

Go to the "Collections" tab, and you will find a new button: "Molecule upload". From now on, all the cool stuff available at mcule.com are not limited for the mcule database. If you have your in-house database or have designed some virtual libraries you can upload them and run the searches and screens on your own libraries. To learn more about user collections, again, check the mcule documentation.

3. Docking visualization

We have found and implemented a great Javascript 3D visualizer: GLMol. After docking, there will appear a "Visualize pose" link, which will display something like this:

Residue labeling has been also implemented. We continue working to further improve this visualization, but the user experience of the current version is already better than any WebGL molecule viewer (of course I'm biased, but still...). To get the best out of this, we recommend to run mcule in Chrome browser.

4. New tab: "Applications"

Under this tab, we will introduce a lot of useful stuff. First: Property calculator. Draw a molecule or enter its identifier, then click on "Calculate" and you will see all mcule properties listed immediately. This works for molecules not in the mcule database too.

5. Documentation

I have already referred to our documentation several times in this post. This is because it has been significantly extended and you can find most of the basic information about the mcule system there together with some nice screenshots. If you get in trouble you might also want to check the FAQ page, where the most typical questions and answers are listed.

6. Flexibility

This is not as obvious as it should (or it is probably better if you don't notice anything of this), but we have completely redesigned the screening workflow technology behind the scenes. Why? To be able to get it to the next step: scale the system up to the sky. Now you can really put any workflow step after/before anything, and this makes the mcule technology really unique. We integrate this whole bunch of tools so flexibly, that will enable you setting whatever workflow you want.

What's next?

A lot of stuff as always, but I don't think docking a few million compounds will remain an issue too long. Only for the very few people around the world who are not mcule users yet. Do you know any? Please tell them to join mcule! We honor the loyalty of our users especially those who bring new people. Soon you will find out how much!

Ten presentations later...

Summer is over, so after attending conferences and having some holiday, we are back to the mcule headquarter. We have made lots of new connections, talked to many people and got great feedback on the current status of mcule.

ACS was very intensive as always, me and Ferenc had 4 oral and 5 poster presentations, which you can check here. The most interesting topics for me were the ones trying to offer new strategies to improve the productivity of the drug discovery pipelines:

Physicochemical property profiles
One significant direction is to improve the physicochemical properties (or at least not significantly worsen them) during optimization. The presentations of Ernesto Freire and George Keseru emphasized that hits and leads should be optimized enthalpically rather than entropically (i.e. more H-bonds, less hydrophobicity) to get more favourable ADMET profiles (less toxicity, more selectivity, etc.). It is argued that clinical failures are primarily due to the unsuitable pharmacokinetic profile of the drug candidates (too hydrophobic, not soluble, etc.). The reason of the failures is either toxicity (because of the lack of selectivity), or the lack of effect (again caused by the small therapeutic window).

Phenotypic screening
The other interesting direction sounds somewhat contradictory to the previous wave. Phenotypic screening is about finding molecules that showing the exact therapeutic effect we need. It is somewhat against the target-based approach, as it is not looking for compounds acting on a single target. On the contrary, the more targets (involved in the systems biology of the disease) it hits, the better. This approach says just the opposite of the first direction. Non-selective ligands are welcome here and to have an effect on multiple targets one would probably go for something hydrophobic, which will lack specificity. Chris Lipinski argues that most successful drugs hit many targets (e.g. kinase inhibitors).

I'm very much looking forward to see which direction will deliver more new drugs to the market in future.

Philly vs. Vienna

Right after the ACS I attended the EuroQSAR conference in Vienna: nice meeting, great people, interesting talks. Interesting case studies and some new approaches have been presented there. Some of the major software companies were also exhibiting, and we discussed potential integration strategies with them. We are currently discussing the details with many of them, so the list of tools waiting for integration is getting longer and longer. Which is a good thing.

In the meantime, the mcule team has been working hard, and a major release is coming up! Short list of what you can expect to appear on the mcule drug discovery platform soon: first subscription packages, improved visualization (incl. binding site and docking poses), user molecule upload, bulk exact search, product filter, and more.