The long and winding road to a published paper (and lovely crystal structures)

Dedicated to Professor Allan White 1938 – 2016

 

dienedione

Xray crystal structure of the diene-dione (1)

This years theme #ChemTogether is all about our chemistry community.  I’ve chosen this year to talk about our recent paper and how it came to be, and the people involved. This paper covers some work that was done over the course of 25 years. That’s a heck off a long time you say. The second thing you’re likely to say is “how can this work that is so old still be relevant?” And that’s a fair question.  So buckle up, settle in and let me tell you a tale. Also depending on your timezone and inclination, you may want to make yourself a cup of tea or coffee, or maybe a beer. Or you might want to snag a copy of the paper here.

“Stereoelectronic effects on dienophile separation influence the Diels-Alder synthesis of molecular clefts” Martin J. Stoermer, Wasantha A. Wickramasinghe, Karl A. Byriel, David C. R. Hockless, Brian W. Skelton, Alexandre N. Sobolev, Alan H. White, Jeffrey Y. W. Mak, David P. Fairlie, European Journal of Organic Chemistry, 2017, in press.

Some history.

This project was only ever supported by one grant, at the very beginning. The grant application was submitted in 1990 while we were employed by Bond University on the Gold Coast, and with an overseas collaborator who was visiting on sabbatical. At the time Bond was Australia’s only private university, but by the time that the grant was successful, Bond was in trouble financially, and by Christmas the science department had been shut, the academics sacked, and the postgraduate students cast adrift.

By the time the 3D Centre had found a new home at the University of Queensland which eventually, after waiting for the political  fallout to subside took over administration of the grant, I began working on other, more medchem-based projects. This was to be the core focus of the new 3D Centre. And so, while working on our long running HIV protease program, this project was marginalised. Nevertheless I was still tinkering with the system in my spare time.

This pattern continued for a number of years, with the research not getting any more government funding including for me personally several postdoctoral fellowship applications. Occasionally we’d get spurred into action and do a little bit of work and have a minor success or two, but then we’d hit the wall and I’d go back to doing what I was paid to do. Some of this earlier work got published in 2003 and we thought we’d be able to wrap up the newer results up quickly. We did, but the paper got rejected several times in one form or another. Mostly the reviewers thought there wasn’t a complete package.

From the outset we knew that this project would need X-ray crystallography to help guide us in our chemistry, and also to see if we’d accomplished our goals. In this we grew our own crystals and sent them to the team at UWA to get the structures solved. Alan White and his team were a delight to work with in those early days, and we are all the poorer for his passing last year. I can still remember when the fax machine would spring into life when Alan sent through the structures. Yes, by fax. On more than one occasion I had the joyful job of re-typing in XYZ coordinate data by hand as it we couldn’t seem to get the data electronically. Times have certainly changed. As is often the case when projects are not officially funded, but manage to move along in fits and starts, some of the crystal structures were done a little closer to home, by Karl Byriel at UQ’s own chemistry department.

The chemistry.

And so to the chemistry. Fundamentally we wanted to build a new class of rigid hydrophobic molecules, which we grandly defined in the original grant application as “enzyme mimics”. In phase one of the work we wanted to build simple systems based on Diels-Alder reactions of templates such as (1) above to create U-shaped structures, capable of binding very small hosts. One such molecular cleft (below) was shown to bind chloroform inside it’s narrow “binding site”. Others bound units of pyridine, cyclohexane, dichloromethane and water.

nbcav2

A rigid synthetic molecular receptor which binds small molecules

Sadly, the lack of granting support in later years meant we couldn’t move along to more complex systems which we had envisaged as catalysts and artificial enzymes.

One of the more interesting aspects of chemistry in this series of molecules, was the relative lack of reactivity at the carbonyl carbon of templates like (2). Whilst we could relatively easily reduce them to the corresponding diols, they were completely inert to reductive amination, which we wanted to  use to make better diamine chelators. In addition, instead of reacting with Grignard reactions or alkyllithiums in the expected manner, the diene-dione instead gets alkylated four times with, in this case methyl groups.

tetramethylation

Novel tetra alpha-alkylation of the diene dione

The steric constraint of this tetra methylation pushes the two alkene moieties even closer together. I won’t go into more details here, but pushing those two alkenes back and forth by changing the central ring has interesting effects on reaction rates.

Publishing.

The last hurdle is always to get the work published. And as I’ve said above, without funding, it’s particularly hard to get time and money to do that one last experiment that get’s it over the line. I’ve lost count of the number of rejections we’ve had on this over the years, both on this paper and a bunch or related work that still hasn’t found a home. But over the years, the negative and positive comments of reviewers have helped us along, so a big shout out to the often maligned reviewers, who are after all our peers and part of the chemistry community. As many of you know my ill health has enforced my early retirement from the lab, so it has been additionally hard to get this work published. And the final push in this case came when a colleague Jeff Mak came on board with new ideas, perspectives, and importantly, a pair of lab hands. And with the support of my longtime boss Professor David Fairlie, we finally got this one done. There’s more to do, but for now I can look happily at those 5 beautiful crystal structures, and say yes! They’ve been set free.

nbcav-300x260

 

 

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ChemDraw 17: Faster editing, new features, still works with Word

ChemDraw 17 Review Part 1: New features

Test platform: ChemDraw Professional 17 (17.0.0.206), iMac 2011 8GB RAM, MacOS 10.12.6 Sierra; Microsoft Office 2011, 2016; and the latest Apple Pages 6.3, Keynote 7.3.

[Update 4 October: Added a short Youtube video showing the Drawing and Reaction Hotkeys in action]

I’ve spent about a week with the new version of ChemDraw now and have to say that this is probably for me the biggest feature leap for the product since Scifinder integration. My test machine is a comparatively old kit and it has run perfectly well. I should point out again, as I have noted before, that when these new ChemDraw versions come out, they are checked and certified for compatibility with the latest, shipping version of the Windows and Mac operating systems. On Mac, this means Sierra, as High Sierra was only released last week. Whilst I can’t foresee any reason why ChemDraw 17 wouldn’t run under High Sierra, it is not supported at this time. I normally expect formal certification for new OS’s in a *.0.1, *.1 or *.2 release.

The headline features of the new version of ChemDraw are new enhanced Hotkeys, HELM support, Document Tagging (metadata), and compatibility with the latest 64 bit Windows systems. But of course you all want to know one thing: Does it support round-trip editing with Word? In a word – Yes (but more on that later). This short review just covers the new features in the ChemDraw Professional application, which forms just a part of the ChemOffice Suite. As with previous versions which I have covered before, various packages are available for Macintosh and Windows PCs at different price points and features lists. The list of versions at the PerkinElmer SciStore is to be found here.

Hotkeys

The feature that I’m most excited by are the new enhanced Hotkeys. The first thing you’re going to want to do is take a look at the ways Hot Keys have been improved to make drawing of molecules much, much faster. Helpfully, Perkin-Elmer have provided a handy cheat sheet. It’s available under File -> Open Samples-Enhanced Hot Keys Cheat Sheet.

CD17CheatSheet

The Hotkey cheat sheet provided with ChemDraw 17

These enhanced shortcuts will, with practice make drawing structures so much faster. I recommend printing that Cheat Sheet out, laminating it and sticking it to the top of your monitor or pinning it above your desk. Take some time to learn the most common ones such as “3” for a benzene ring and “6” for cyclohexyl. If a significant chunk of your life is spent drawing and editing structures (think thesis writing!) then this will save your hands from repetitive back-and-forth mousing to click on template icons. PerkinElmer and Chemistry World are running a Webinar on the new ChemDraw 17 on October 24th at 4pm (UK time), so I’d check that out if you want to see this in action.

Actually, while you’re looking at that Samples menu take some time to look at some of the others that are included there. Most of these have been there before but they are worth reiterating as really useful starting points for many types of complicated figures. I particularly like the Grignard reaction summary slides made by Roman Valiulin (@RomanValiulin), and the GPCR pathway templates which you can use as a starting point for any signalling pathway you care to draw.

Grignard

Also new in ChemDraw 17 is a really neat new Reaction Hotkey feature. Lets say you have a simple 3 step synthesis with a core component. To generate a quick reaction scheme, simply select any object, hold down the command key and use an arrow key to automatically copy-paste a duplicate molecule in the direction you chose, including an arrow. So in the example below I drew the initial biphenyl, and then used “Command-Right Arrow” to create the first reaction, then  “Command-Down” and  “Command-Left” to generate the other two elements of the scheme. I then went back and using the hotkey “1” added a methyl group which was to become the changing element at the para position. The amino and iodo groups can be added without clicking and editing the newly created atom by simply using the “n” and “i” hotkeys respectively in mouse-over mode. The nitro group was the only thing that had to be edited manually.

Reaction Hot Key

HELM (Hierarchical Editing Language for Macromolecules) Support

What is HELM? Think of it as a kind of SMILES for biomolecules. Chemists use SMILES strings as a convenient way to move chemical structures from one format to another, or from database to database. Typically SMILES notation is used for small molecules although they can be used for larger biomolecules. The HELM project was started by scientists at Pfizer as a way of getting complicated biomolecules and their derivatives into a searchable form for corporate compound databases. The HELM project is trying to provide a way of systematically representing complicated biomolecules such as post-translationally modified proteins, peptide-DNA/RNA conjugates, glycosylated proteins, cyclic peptides and all of the above containing a range of synthetic and semi-synthetic amino acid monomers, and fluorescent tags.

Hexaleucine in HELM editor notation, HELM string, and expanded structure

Chemdraw now provides a way of creating and sharing HELM strings for these systems. If you’ve ever used ChemDraw’s peptide or DNA drawing tool (The BioPolymer Toolbar), the new HELM tool will feel familiar. The tool now provides tabs with which you can create the components of your molecule, lets say a short peptide sequence and a fluorescent tag as separate objects. In the sequence of pictures below below I have drawn hexaleucine, and an Alexafluor tag (Step 1), and then connected the objects using normal chemdraw bonding methods (Step2). Then using the Expand label tool (Step3) you can see the full molecule (Step4).

There are a few quirks in the HELM database currently. For example in the the CHEM tab of the HELM toolbar below, if you look closely you will see a few items that are named somewhat differently. For example the shortcut for adding an Alexafluor tag to a peptide has the abbreviation Alex and the mouseover name calls it Alexa Fluor 488 NHS ester, which as peptide chemists know is the reagent used to introduce an AlexaFluor tag (The N-hydroxysuccinimide ester), not the name of the tag itself. There are also somewhat confusingly two chem entities abbreviated chol.

HELM1

Step 1: Using the HELM toolbar to draw the components as separate objects

HELM2

Step2: Draw the bond between your desired positions

When you expand the abbreviations, ChemDraw also leaves a small label adjacent to each element (which I normally immediately delete)

HELM3

Step3: Using the Expand Label and Clean up tools.

HELM4

Step 4: The tagged peptide structure after clean up

Document tagging – User-defined metadata

Document tagging is a way of adding user-defined metadata to your ChemDraw documents, to enhance their searchability.  It is invoked in ChemDraw 17 from the Edit  -> Document Properties menu. If you have started from an empty document and not a corporate template then everything you see in the initial dialog is empty. There are no predefined fields so you can add items to the list pretty much as you want. I can imagine that in corporate settings there may be fields for user, compound identifiers, Project codes, company and division name etc. When you add a property, you can define it as being either optional, recommended, or compulsory to have the field filled.

Customisable metadata entry in Document Properties dialog

In academic settings this feature may be less rigorously adhered to as I can see that it would take a great deal of compliance. I can see the potential benefits though in chemistry groups where more than one person is working on a project. You could set project keywords, and you of course want to know who created the document in the first place. On their product page, Perkin Elmer note that these metadata are searchable by third party software including Attivio and Elastic. It will be interesting to see if they will also be searchable from within MacOS (Spotlight Search) or Windows Desktop Search.

Once again, PerkinElmer and Chemistry World are running a Webinar on the new ChemDraw 17 on October 24th at 4pm (UK time), during which they are sure to be showcasing these features live.

ChemDraw 2017 Review Part 2: Round-trip editing, a deeper look.

Whenever a new version of ChemDraw comes out the first question I get asked is always “Does it break round-trip editing with Word?” If I may steal for a moment a paragraph of my initial review of the 2016 release:

Much of this review is concerned with it’s interoperability with Microsoft Office 2011 (specifically Word), as probably the vast majority of theses and papers in (organic) chemistry written on Macs would be written with this or older versions of Word as leapfrogging software package upgrades have a long, and sometimes chequered history together on the Mac. For my previous posts on this subject see here, here, here, and here.

I am happy to report that this new version of ChemDraw does support round-trip editing with both Office 2011 and 2016 (as part of Office365). It behaves exactly as expected. Objects you’ve pasted in previously can be copy-pasted back into ChemDraw and edited, then pasted back into Word or Powerpoint.

Round Trip editing with Word 2016 and ChemDraw 17

Round trip editing with Powerpoint

Not such great news is that round-trip editing with Apple’s suite of Productivity apps, Pages and keynote  is still broken. It was broken during the beta cycle with an earlier version of Pages (v5.6.1) as well so it’s not just the High Sierra-ready versions that have broken something. It seems that unfortunately due to the way that objects get transferred to the clipboard in Pages/Keynote, those objects are not editable when they get pasted back into ChemDraw.

That’s the short version but for those who are interested, I dug a bit deeper and uncovered a few clues about what parts of the process do work.

Steps taken:

1) Open ChemDraw 17

2) Open ChemDraw file  “2NaphKKRaldehyde.cdx”

3) Select structure

4) Copy to Clipboard

5) Open Pages 6.3

6) Paste item

7) Save Pages document “CD17Pages6test.pages”

8) Quit Pages

9) Open “CD17Pages6test.pages”

10) Select the structure,

11) Copy to clipboard

12) Open ChemDraw 2017

13) Paste item into new empty ChemDraw17 document

14) Structure is not editable, see object with blue boundaries only

Once again, the blue bounding box means it’s no longer editable.

Interestingly however, the required vector graphic information is present in the Pages file, as evidenced by the fact that whilst within Pages if you right-click on the ChemDraw image you can choose the Edit Mask function:

Applying the Pages Edit Mask function

And you are then provided with the Pages Mask popup, which includes a resize by slider function. Somewhat weirdly when you drag the slider to increase the size the structure initially expands beyond the bounding box, but when  you finish, the popup disappears and you’re left with a truncated, but scaled up portion of the structure.

This truncated chemical structure was then pasted back into ChemDraw and unfortunately was still not editable, but did appear nicely scaled back in ChemDraw, and printed with no blurring of the lines.

Therefore it seems apparent that all the vector graphic information is present in the Pages document, but only some parts of it are transferring to the clipboard. Investigating further within ChemDraw 17, this newly pasted truncated structure behaves in some ways like a regular ChemDraw object. The initial structure above was created using the ACS template, but if you take the new truncated, but scaled up fragment back to ChemDraw and paste it in, it pastes at the scaled size. BUT, if you then use the “Apply Object Settings from…” function and choose a different template, in this case the RSC two-column format, it attempts a rescale, but gets it wrong. So there’s sufficient information placed back in the Mac clipboard from Pages that it knows it has scalable bonds, but can’t convert the information into an editable structure.

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Pymol 1.8.x now fetches mmCIF files by default and shows missing residues in Sequence View

Long time Pymol users will be familiar with the fetch command by which it retrieved the selected file from the Protein Data Bank (PDB). Up until version 1.8, Pymol fetched the PDB version of the file by default over the mmCIF option, which the biomolecular crystallography community has long been advocating due to some deficiencies in the legacy PDB file format. Now however, Pymol fetches the mmCIF version by default and has a new default behaviour as well. When viewing the sequence bar,* Pymol now show the residues that were missing in the crystal structure, whether due to insufficient resolution or electron density. These are now displayed in grey lettering in the sequence bar (Figure 1).

Figure1. Pymol imports mmCIF files now by default with the fetch command, and displays missing residues as described in the metadata

There are also significant differences in how water molecules are listed. Previously water molecules were associated with each subunit or chain within the PDB file. In figure 2 I have loaded a second copy of the 3e90 structure which I had downloaded as a .pdb file. I had to rename it to 3e90a.pdb otherwise Pymol would have assumed it was a second state of the molecule which I did not want. You can see clearly here that for the PDB version, the water molecules associated with chain A are listed after the amino acids.

Figure2. Second copy of crystal structure manually loaded from a previously downloaded PDB file.

Similarly the water molecules and ligands associated with the PDB file are shown at the end of chain B (Figure 3). Whereas the initially loaded mmCIF file puts them all at the end of the line as separate objects, along with the extracted ligands and salts (Figure3).

Figure 3. in mmCIF files, ligands and water molecules are listed as separate chains, whereas with PDB files that are associated with a protein chain

 

I have not yet worked out a way to undisplay those missing residues short of deleting them, and they can cause issues when trying to align different structures. For example in Figure 4, the alignment of the missing residues in Box A with all the water molecules of chain A doesn’t make a lot of sense. On the other hand, the small Box B shows  how the mmCIF file conveys useful information about the residues that are missing in that portion of the PDB version of the structure.

Figure 4. Alignments in Pymol can be problematic when missing residues “align” with water molecules

 

This way of displaying missing residues quickly gets confusing when overlaying multiple structures, in the case of Figure 5, multiple versions of the NS2B/NS3 protease from West Nile Virus. For the moment I would recommend downloading the PDB files individually as PDB files and hold off switching to mmCIF if Pymol is your principle viewer.

Figure 5. Using mmCIF versions for multiple alignments with several deletions represented by grey lettering can become confusing

 

Test Platform: MacBook Pro (2011), MacOS El Capitan 10.11.3, Pymol v. 1.8.4.0

*To turn the sequence bar on you can either press the S button third from the right at the bottom of the screen, or use the seq_view command.

The sequence bar toggle button

 

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When in Pymol, don’t call your model “model”

Sometimes it pays to read the blurb that loads in a textport when software loads.

Folks, there is an inherent problems when viewing your Swissmodel results in Pymol. Like many people I usually look away from the screen when I boot a program as I know it will often take a few seconds while either a boot screen appears, or more commonly with molecular modelling programs, a bunch of text scrolls by in the terminal, or in a textport window somewhere in the GUI.

Turns out that in the case of Pymol I should have been paying a bit more attention. I am an enthusiastic user of Pymol and may be guilty of proselytising a bit in it’s favour on Twitter. When Pymol boots, a lot of information scrolls by in it’s textport

 

Pymol boot screen

 

As a part-time homology modeller I use a range of software, and recently I’ve been using Swissmodel frequently. I like it quite a lot as it’s:

  1. Free
  2. Easy to use
  3. Web-based and frequently updated
  4. Gives good models as starting points for more rigorous study

However for years there’s been one aspect of results from Swissmodel that have been infuriating. When you download your results you get a lovely html-based nest of folders containing the different models produced. Unfortunately it names every model “model.pdb”. Not even model1.pdb, model2.pdb…

Swissmodel output files

When you load any of these results in Pymol a whole bunch of operations are blocked. You cannot use the “actions” menu, or even “Show Cartoons”. Over the years I’ve used a couple of workarounds. The simplest is to rename the model to something more useful. It should have dawned on me that there was something intrinsically wrong with the name model.pdb but I didn’t bother to pursue it.

Using the Pymol Actions dropdown to extract the selection to a new object

If I forget beforehand to rename* the file I simply used to use the Pymol “extract object” feature to take the entire molecule out of the file “model”, and then continue work. Now if I had bothered to look more closely at the textport I would have seen that:

Executive-Warning: name “model” collides with a selection language keyword.

Update: It is of course easy to rename model.pdb using the “set_name” command in pymol to something that allows you to keep working, rather than going through the trouble of extracting into a new object as I had been doing. The correct syntax is:

set_name model, newname

It doesn’t help to know this now of course, I still have to use a workaround. It would just be nice if there was an option to have the 16 different models that Swissmodel produced in this case named something different (like model1, model2, model3…

POSTSCRIPT. I hope that this brief post doesn’t sound like too much of a whinge. I aim to write a bit more about Swissmodel, which is an excellent resource for people looking at getting into homology modelling in particular in the near future. If you have any questions about today’s post, or about Swissmodel, leave a comment or you can always send me a Tweet @MartinStoermer over on Twitter.

POSTSCRIPT. I saw this great tip from Cult of Mac for bulk renaming files with renumbering in the Mac Finder, which I didn’t know about. It works great, even on nested files in folders.

bulkrenamerenumber

The inbuilt bulk rename/renumber tool in the MacOS Finder

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Major upgrade to WebCSD – The small molecule crystal structure database

[Update 16th June: Added Note about Pymol 1.8.4]

The new version of WebCSD has arrived and with it, a few new important features, such as improved substructure searching, and advanced text searching. The Cambridge Crystallographic Data Centre (CCDC) houses the the Cambridge Structural Database (CSD), a repository of over over 875,000 small molecule structures from x-ray and neutron diffraction analyses.

Growth in the CSD. Graphic copyright The Cambridge Crystallographic Data Centre http://www.ccdc.cam.ac.uk. The Cambridge Structural Database, C. R. Groom, I. J. Bruno, M. P.
Lightfoot and S. C. Ward, Acta Cryst. (2016). B72, 171-179 DOI:
10.1107/S2052520616003954

Traditionally, use of the CSD has been by institutional licensing of the desktop client Conquest, and by downloading periodic updates. The current release is May 2017. Recently a Java/Web interface WebCSD has become available for use, which contains fewer features compared to Conquest, but which is useful for accessing structures if you are out of the office or working from home. Unfortunately, I frequently had problems with the previous version which used to throw up lots of erroneous Java errors on Mac, claiming that the user had an out-of-date Java version. Happily this annoying bug seems to have gone with the new version.

Java Error with WebCSD v1.1.2 on Mac

Another confusing thing about the old WebCSD was that it used a different login system from the CCDC data deposition interface, requiring crystallographers or IT departments to maintain separate logins. In the new version you log in with your data deposition username/password at the main CCDC home page. The first thing you will notice is that the new CCDC home page now has two large button options:
Deposit structures and Access Structures.

new CCDC home page

Choosing Access structures takes you to the new WebCSD text and structure search interfaces in a familiar tab format.

Text Query Interface in the new WebCSD

Substructure search in the new WebCSD

I first gave it a quick try in text mode looking for structures of my current favourite mushroom toxin cyclic peptide α-amanitin. The results page has all the structures preselected in a tickbox format and encouragingly there is a “Download Selected” button.

Hits Page in WebCSD

This may not seem like a big deal but one of my major gripes with previous versions of WebCSD was that it was not possible to do a bulk download of hits. For that you have to use the Conquest interface, something that is impractical to do off-site.

So finally you can download all the hits, but currently only as a multiCIF file. This is not the easiest option but better than nothing. I’m currently trying to find reliable ways to convert or read multiCIFs. Pymol loads them all but only puts bonds in for the first entry (see pictures below). Update: Newer versions of Pymol (I used 1.8.4) read in all the files in a multiCIF correctly.

MultiCIF files opened in Pymol (v.1.6). First entry shows bonds, later entries just show atoms.

New versions of Pymol (v.1.8.4). show all atoms and bonds correctly*

Schrödinger’s Maestro only reads only first of a multiCIF file. The CCDC’s own software Mercury reads them all into the viewer window, from which you can select and export the files in a variety of formats, but you still can’t bulk export them all to another format.

Amanitin hits from WebCSD displayed in Mercury

I next tried searching for a substructure, a cyclic octapeptide equivalent with four thiazoles. Excuse the drawing, I’m still coming to grips with the interface and rotating etc. This came up with one hit, which happens to be a symmetric compound with four prolines occupying the remaining four amino acid positions. (Link to paper)

Substructure search interface. Had trouble finding rotate or cleanup tools

Nicely, there is a JSmol rotating 3D model of the structure as well. This hit also shows how this class of modified peptide macrocycles frequently bind solvent molecules and metal ions, In this case I have caught the rotating JSmol at the right angle to see a nice molecule of acetonitrile bound in the centre of the macrocycle.

WebCSD substructure hit interface

This has been only a very short overview of the new version. Stay tuned for anything else I discover. In particular one of the best things about new version is that is much much faster. I look forward to the products continued evolution, particularly the ability to extract hits to SD files, which is a standard feature of the desktop version.

*I should note that multiCIF files often contain coordinates for disordered atoms and these may display weirdly in Pymol. Pymol uses distances to estimate bonds, so some downloaded structures may appear to have chemically unfeasible connectivities.

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New initiative: The Molecular Sciences Software Institute (MolSSI), based at Virginia Tech. via @ACSPublications

“A new computational chemistry software institute, the first of its kind funded by the National Science Foundation, aims to bring software development in the field up to speed with rapid advances in computer hardware.

The Molecular Sciences Software Institute (MolSSI), based at Virginia Tech, celebrated its launch with a reception on Tuesday at the American Chemical Society national meeting in San Francisco.”

I haven’t had a good look at this yet, I just saw this over at the ACS Meetings page. This looks like a really interesting initiative from the NSF. I can’t see any current job openings on the site, the last round closed in November 2016 and the Fellowships in February 2017. Something to keep an eye out on for when the next round opens.

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ChemDraw, Chem3D dropped from iOS App store

☹️ I missed this one back in January, but I could sense it was coming. CambridgeSoft have dropped the iOS apps ChemDraw, Chem3D, and CDSL from the App Store. (admittedly I hadn’t heard of the last one at all). Together with this, the “Flick2Share” feature has been killed off. I never really used Flick2Share but it seems that PE are putting all their efforts in the sharing space into the updated ChemDraw Cloud, which I also haven’t really used yet. I hope to get around to fully evaluating ChemDraw Cloud at some point and reviewing it here.

deathofcdapps

ChemDraw, Chem3D, CDSL iOS Announcement © Cambridgesoft / Perkin-Elmer

I’m sad that the iOS apps are gone, particularly ChemDraw. I like the ability to quickly share structures to social media, particularly seeing as the desktop versions struggle to easily produce GIFs that retain resolution in web browsers, especially  on Twitter, and in 3rd Party Twitter clients,

[Update 2 March] However, if you have downloaded the apps to your iPad they will continue to function. Testing this morning on my rapidly ageing iPad3 the last-downloaded versions (ChemDraw 2.01, Chem3D 2.02) worked OK, except that on startup you may see an oblique message to the effect that “a sharing option could not be enabled”. I forgot to screenshot it but I presume this means Flick2Share.

 

So here is a summary of what still works. ChemDraw:

  1. Drawing, editing, saving, and (some) exporting of structures
  2. Save picture to Camera Roll
  3. Dropbox export (PDF, PNG, CDXML) works fine as previously
  4. Twitter export
  5. Export via email

What doesn’t work:

  1. Flick2Share

 

img_1207

Twitter sharing in ChemDraw for iPad still works

 

Chem3D was always a somewhat limited product compared to the desktop version, and never gained any additional features after my original mini review. This limitation was somewhat compensated for by virtue of being free. Importing structures could only be done through iTunes or downloaded protein structures from the PDB. Chem3d for iPad is a viewer application only. There are no molecular mechanics options available at all, and analysis options are few. But after a brief test the list of what works and what doesn’t is as follows:

  1. Viewing and importing of structures from the PDB
  2. Save picture to Camera Roll
  3. Twitter export
  4. Email export

What doesn’t work:

  1. Flick2Share
  2. Dropbox Export
Chem3D Twitter export also still works.

Chem3D Twitter export also still works.

Actually I don’t recall Dropbox export ever working for Chem3D, whereas it works fine for ChemDraw. As of this morning choosing Dropbox as the export function simply flips you out to the Dropbox app, if installed, to the default root directory listing page, and no option to name the file or specify a location. It just sits there until you go back to Chem3D. Nothing is ever written to Dropbox. Personally I have always preferred Pymol for visualising proteins for use online and in print,  so the loss of Chem3D for iPad isn’t as big of a deal for me as ChemDraw.

I was happy to pay around $10 for ChemDraw when it came out so I’m disappointed that it’s been abruptly dropped. It’s a peculiar strategy for CambridgeSoft/PE who evidently see ChemDraw Cloud as the future, particularly as everyone else in the app space seems to be trying to drive people away from web services and onto apps. Witness the endless pop-ups in Safari on every other web page imploring you to download and view their content in their app. An annoying UI “feature” that I earnestly implore Apple to kill ASAP.

When these apps originally appeared I saw them as principally teaching tools, given the reduced set of features and lower price point. With tablets becoming common in schools I saw possibilities for teachers and students flicking structures back and forth in pop quizzes  etc. A few people have contacted me wondering about this too, but I have absolutely no idea of what the uptake of this was in schools. Obviously PE has that information and made a business decision to drop it. I’m not yet convinced that ChemDraw Cloud is going to fit that school usage demographic either. In it’s current form its seems placed more towards the higher, content creation end of the user spectrum.

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