Torch Released

We are delighted to announce the release of Torch, the next generation of FieldAlign, an intuitive 3D molecule designer. Torch brings new capabilities to medicinal chemistry desktops while maintaining our focus on easy to use, easy to learn software that produces meaningful results within minutes.

Existing FieldAlign users can upgrade to Torch for free. If you have not already received your new license file then please let us know. If you’re new to our molecule design software you can get a free one month evaluation here.

In common with Forge and Spark, Torch uses the next generation of our proprietary XED force field to describe molecules and their interaction from the protein’s view point. Using Torch gives medicinal chemists a unique insight into how molecules relate to each other and to the target protein, enabling a deep understanding of structure activity relationships. However, understanding is only half of the equation. Torch brings a powerful molecule editor and sketcher that chemists use to design their next molecule. The editor provides immediate feedback on each design giving a rapid progression of idea to synthesis.

Specific additions in Torch are:

  • New molecular mechanics force field (XED3).
  • New protein importer to read and process pdb files into protein and reference molecule.
  • Download pdb files directly into Torch and view protein-ligand interactions.
  • Display and use Forge QSAR models in the scoring of molecules.
  • Improved molecule reading to give fewer clicks and more intuitive operation.
  • Measure distances, angles and torsions, automatically display intramolecular H-bonds and atomic clashes.

Intelligent Automatic Design of Bioisosteric Analogs

A program for automatic identification of bioisosteric analogs, scaffold hopping and fragment growing called IADE has been developed at Novartis Institutes for BioMedical Research. The system frees modelers from repetitive and time consuming tasks and allows them spend more time on creative work: evaluating and selecting the best ideas from automatically designed structures.

Cresset’s command line FieldAlign (now part of Forge) software was used by Novartis as follows:

  • To generate a set of representative conformations using standard methods from which the conformation most similar to the template ligand is identified.
  • To find the best alignment based on superposition of positive, negative, hydrophobic and steric fields around the molecules.
  • For similarity scoring (employing an equal weighting of field and shape similarities).
  • For conformation search and subsequent identification of the most similar conformer.

Novartis’ work has been published in J. Comput. Aided Mol. Des, 26, 1207-1215 (2012) and can be read here.

Peter Ertl, Novartis and co-author of the above article, was the winner of Cresset’s Design a Molecule Competition in Fall 2011 and presented the work at Cresset’s 2012 European User Meeting.

Find out what’s new with the Cresset product line up.

Review of Cresset European User Group Meeting June 2012

Our scientific programme reflected the wide range of scientific fields involved in drug discovery and the depth of breadth of scientific knowledge that goes into developing software for in silico research. The talks ranged from the force fields involved in protein-protein interactions to the use of NMR technology to understand drug metabolites. Below is a review of each presentation. If you would like further details of any presentation please contact us.

Dr Jon Mason of Heptares opened the day’s scientific talks with an informative overview of his work on the energetics of water networks in proteins. Having worked in this field for over 25 years, he has reached a point where he has found that the computational mapping of water energetics in a protein target has a high correlation with druggable binding sites for targets, or at least with ligandable targets.

Dr Mark Mackey, Cresset’s Chief Scientific Officer gave an overview of the new science that Cresset has been working on, including how conformations are generated, new sampling methodology for 3D QSAR, advances in fragment growing technology with the option to merge results from multiple ligands, and finally an updated force field, FF3 which refines and improves Cresset’s existing XED force field. He also introduced forgeV10, Cresset’s new 3D QSAR environment.
Download the presentation here.

Dr Peter Ertl, Director of Cheminformatics at Novartis shared his Intelligent Automated DEsign (IADE) method for bioisosteric design. His automated fragment replacement system firstly identifies bioisosteric fragments for a given compound and replaces them iteratively to generate several hundred analogs. These are converted to 3D structures using CORINA. Reasonable conformations are generated using Cresset software and the conformation most similar to the target is identified using FieldAlign. He used this method to design the winning molecule in Cresset’s ‘Design a Molecule’ competition in October 2011.

Dr Andy Vinter, Cresset’s Chairman updated us on how he has used the XED force field to normalise proteins and gain insights into the actions of agonists and antagonists. He reminded us that atomic charges do not sit on the nucleus, as some force fields approximate, but rather the real electrostatic charge varies close to the atom, as reflected in Cresset’s unique FF3 force field.
Download the presentation here.

Drug repositioning is an increasingly popular area of drug discovery. The increasing costs of R&D and decreasing return on investment has lead many companies to focus on finding new opportunities based on existing drugs and their templates. Dr Alan Rothaul gave an overview of structure and non-structure based methods of repositioning and showed how structure based re-profiling through fragment swapping can feed into new compound discovery. He pointed out that new intellectual property has to be established and that this is often determined through reformulation.
Download the presentation here.

Dr Ute Gerhard of the University of Hertfordshire demonstrated how the power of NMR and mass spectrometry analysis are used to determine the structure and concentration of drug metabolites. The detection limits for state of the art NMR are now where mass spectrometry was ten years ago. NMR can be used to successfully identify potentially toxic metabolites so that only good quality drug candidates are progressed through the discovery process.
Download the presentation here.

Optibrium and Cresset recently announced a collaboration to combine the power of Optibrium’s StarDrop with Cresset’s FieldAlign. Dr Matthew Segall of Optibrium gave an overview of multiple parameter optimization (MPO) for drug discovery, as delivered in StarDrop. Drug discovery demands that chemists make confident decisions based on complex multi-dimensional data. The challenge is to optimize the vast quantities of data available, while making allowances for data accuracy and weighting.
Download the presentation here.

Dr Ronnie Palin of Redx Pharma gave an overview of their approach to drug discovery by discussing novel lead identification using similarity scores. He explained the best starting point is existing drugs since they are known to hit the target and the majority of the optimisation has been done. Their Redox Switch technology is used to change the chemical structure, then Cresset FieldAlign was used to rank the Redox Switch ideas to give the rapid identification of hits in unexploited IP space. Based on this work they have filed patents in multiple therapeutic areas. He gave the example of changing carboxylic acids while retaining activity. Their anti-viral project started with the known anti-flu compounds zanamivir, oseltamivir and peramivir. Their chemists generated ideas to replace the carboxylic function, then Cresset data was used to score the results and the best results were optimized. The found good correlation between the predicted binding and the inhibition of neuraminidase.
Download the presentation here.

Dr Raj Gosain of the University of Southampton told us about two recent projects that his students have carried out using Cresset software to virtually screen compounds of interest against the ZINC database of screening compounds. In the first case a student started from an unusual squaramide structure, which when it was run through the database identified a new compound that whilst having lower activity was actually a more selective hit. Dr Gosain pointed out that they could not have arrived at this compound with any method other than Cresset software. The second example was looking for an inhibitor of the anthrax lethal factor. Starting from a compound with little potential IP due to existing patents they were able to find a tractable starting point for medicinal chemistry, which had novel structure and was clear of existing IP.

This stimulating mix of talks covered an engaging mix of disciplines including pharmacology, medicinal chemistry and computational chemistry. Dr Rob Scoffin, CEO of Cresset summed up the day by reviewing how Cresset has grown and changed over the last year: “Cresset’s customer base is expanding, there has been rebranding with new product names and organizations. However, our core focus remains the same: to provide the best science with the best customer support”.

Winner of Design a Molecule Competition Spring 2012

Spring’s ‘Design A Molecule Competition’ was Cresset’s fourth and the third to have an anti-malarial flavor. Contestants were asked to design a molecule with a target relevant to antibacterials and anti-fungals.

Cresset was delighted with the response to the competition. The resultant entry molecules were ranked relative to the original bioactive/bound conformer using Cresset’s ‘3D Molecular Field Similarity’ in FieldAlign and then judged on synthetic tractability and drug-likeness. Novelty was also factored into the ranking by imposing a 2D similarity penalty.

Winner: Congratulations to Albert Kooistra (PhD student in the division of Medicinal Chemistry of VU University Amsterdam), the winner of an iPad!

Albert ‘s winning entry won on the grounds of its combination of simplicity, 2D dissimilarity from the template, fit to the protein pocket and (more subjectively) on its tractability and logP / TPSA profile. The design is simple and compact with a nice fit to the pocket. The zwitterionic piperidine fragment provides the necessary twist in the molecule – that is normally induced by ortho-chloro substituents in the parent Triclosan – and potential backbone H-bonding interactions. The addition of this polar fragment also serves to counter the overall high lipophilicity exacerbated by the alkyl thiophene substituent (although maybe too far?).


Image: Winning entry Albert Kooistra, 2D and 3D (modelled in ENR)

In response to hearing about his success winning the competition Albert said: “I really enjoyed competing and using your FieldAlign tool again. Compared to the previous competition (in which I was kindly awarded a 2nd prize) this was a whole new challenge due to the different reference molecule and of course the different target.”

There were many other good entries which were running very close on Albert’s heels, namely: Anthony Nahoum (Strathclyde University) who submitted a couple of nice examples; many imaginative and diverse entries from both Chris Swain (Consultant) and Andrew Lima (4th year student Cardiff University). Well done to all!

Cresset has no commercial interest in exploiting IP from its competitions and so with consent from contestants we are very happy to disclose the winning structures.

Cresset’s Design a Molecule Competition is not only a great way to hone your molecule design skills, but to generate potential leads in the fight against malaria, which is why any IP generated from the competition will be donated to a not-for profit working on this very worthy cause. In preparation for next time you can familiarize yourself with the last competition, or download a demo of our products.

What’s new with the Cresset product line up?

We have made some major changes to the names of our products recently and are thrilled to introduce a new suite of Next Generation Chemistry Software. The suite encompasses five products: Forge, Torch, TorchLite, Blaze and Spark. This new product line up is designed to fit more closely with your computational and medicinal chemistry needs and we encourage you to take a look and let us know what you think.

Some of the products have simply been re-launched with fire-themed names like Blaze and Spark, but others will show significant changes over previous products and now include exciting new features.  If you’re already using Cresset software or you’ve grown accustomed to the old product line, you might want to take a look at the product guide below to see how things have changed. We’re launching the new products together but it will take a few weeks for the developers to finalize all the releases so please bear with us during the change over.

Old Product Name New Product Name Description and Features
FieldTemplater and FieldAlign together Forge Forge is a powerful computational suite to understand SAR and design. It brings together all the functionality of FieldAlign and FieldTemplater together with new science and new capabilities. It helps you:

  • Decipher complex SAR and communicate the results.
  • Design better molecules based on predictions you can trust.
  • Prepare detailed pharmacophores.
  • Virtually screen 10 000 compounds on your desktop.
  • Generate ADME and off target activity profiles.
FieldAlign Torch Torch is a powerful design and 3D SAR tool for medicinal chemists. Torch represents a new opportunity for our medicinal chemistry customers to use a product that is dedicated to the tasks that you want to do.  It helps you:

  • Perfect the design of new lead compounds, exploring a range of lead optimization ideas.
  • Get the most from your lab time by prioritizing compounds for synthesis.
  • Design focused libraries for synthesis or initial screening.
  • View ADME profiles and off-target activity prediction on all designs.
  • Use powerful predictive QSAR models from Cresset’s Forge.
FieldView TorchLite  TorchLite is a free 3D molecule viewing, editing and drawing tool.  It helps you:

  • Sketch your chemical series to study how field and activity patterns are related.
  • Import and compare up to 10 000 compounds from SDF, MOL2 or Cresset applications.
  • Convert from 2D to a minimized 3D conformation.
  • Clone and compare molecules side by side or overlaid using Cresset’s unique field technology.
  • View virtual screening results.
FieldScreen Blaze  Blaze is an amazing ligand based virtual screening tool.  It helps you:

  • Increase the diversity of your project’s leads and backups.
  • Jump into new areas of chemical space.
  • Improve the lead-like properties of hits.
  • Virtually screen 10 million structures in a few hours.
  • Design diverse libraries of compounds for synthesis or biological screening.
FieldStere Spark Spark is an exciting and powerful way of generating novel and diverse structures for your project. It helps you:

  • Generate highly innovative ideas for lead molecules in new areas of chemical space, overcoming the ‘chemotype trap’.
  • Use filters to find the results with the right mix of physicochemical properties and biological activity.
  • Tailor results by selecting the chemistry allowed for the replacement moieties.
  • Visualize results in detail side-by-side, or cluster similar chemical scaffolds.
  • Search for moieties from real, published and unexplored compound databases or create your own custom databases.
Xed Tools Xed Tools Nothing’s changed here!  The XED molecular mechanics force field is still at the heart of Cresset’s field technology and you can still use Xed Tools for conformation generation and ligand minimization.

Still have more questions?  Take a look at the FAQs below, or contact us to learn more about the product line changes and how they work for you.

I already use some of the old products.  What happens to my yearly license?

Nothing changes for now.  You can continue to use your current software license(s) without any interruption in service. When your license is up for yearly renewal, we’ll be in touch to see how your needs align with the new products and then you can decide which products work best for you.

Do these new products work with the same operating systems and interfaces as the previous product line up?

Yes, all of new products work exactly the same way as they did previously.  The table below gives you a good idea of which products work with which operating systems and interfaces.

Operating Systems Interfaces
Product Windows Linux Mac
Xed Tools

I just tried a demo of one of the old products. Do I need to try a new demo the new products too?

That depends on which product you’re interested in. If you’ve previously tried FieldTemplater or used FieldAlign and wanted to do more then you will definitely want to check out a new demo of Forge because we’ve added lots of cool new features that were designed specifically with computational chemists in mind. If you’ve tried a demo of FieldStere, FieldScreen, XedTools, or any of the interface options you probably don’t need a new demo right now because all we’ve changed is the product name.   Feel free to contact us if you have questions about your product demo.

Why did you rename the products with fire-themed names?

We’ve been planning to align our product line up more closely with your needs for a long time, and with the launch of Forge, we decided it was also a good time to update a few other things.  Plus we love the fact that our fiery Cresset logo now matches our new product names!

Some of the links on your site don’t work anymore.  What’s happening?

Sorry, this is our mistake and we apologize for the inconvenience. We’re doing our best to ensure that our website gets updated right along with the product changes but you’ve obviously found a mistake.  If you find a broken link, or other problem, please let us know and we’ll fix it right away.


Forge Sneak Peek

We’ve been working steadily over the last six months to improve on our offering to Computational Chemists and other power users. The result is Forge, a new application that combines all the features of FieldAlign and FieldTemplater into a single new package and adds a heap more of the functionality you’ve asked for. We are really pleased with the result and as we near release we thought we would let you in on the secrets that are coming soon.

The primary role of Forge is to help with decoding structure activity relationships and generating new molecule designs with meaningful activity predictions wherever possible. On the design side we’ve revamped the molecular editor to give you the flexibility to design molecules using fields in an interactive environment. Take a look at the screenshot below:

Forge Molecular Editor

The screenshot shows the new drawing buttons on the left with ring templates which will please all those that asked for them and make drawing far less painful. There is a new button on the right “Align” will align the molecule that is present in the editor to the reference molecule giving you immediate feedback on a new design and giving you the ability to manually edit alignments. We call this “score while you draw”!

To enhance the understanding of structure activity relationships in your molecules we have introduced automated analysis of field patterns using a QSAR method and new alignment methods to give you more ligand centric views as opposed to the protein centric view that we have traditionally generated. The QSAR that we are introducing is a completely new 3D method that uses the field points around your ligands as sampling points for the field of a ligand. In effect we generate a irregular, non-lattice grid around the ligands which is then used to generate field samples on every molecule in the training set. Using PLS acrosss this dataset gives an indication of which regions of the field are contributing to the observed changes in activity but also generates a way of predicting activities for compounds of unknown activity. The QSAR model that you create can be exported to be used by others or used to help the design process including in the “score while you draw” feature. The QSAR is completely integrated into Forge with all the statistics that you would expect from a method of this type (see the screenshot below for an example). Of course 3D QSAR is not a panacea but in our hands this methods has greatly enhanced many of the customer projects that we have worked on.

Forge screen shot showing model information

Underlying these functionality improvements is a new version of our XED molecular mechanics force field that introduces some fundamental changes as well as field pattern improvements. The biggest change in the force field is the introduction of a completely analogue nitrogen atom type that can transition from planar to pyramidal depending on the degree of hydbridisation with surounding atoms.

Lastly, Forge is firmly a Cresset application and comes with the intuitive user interface that you have come to expect from us, plus  a comprehensive wizard to guide you through the process of setting up experiments.

Forge showing a FieldAlign type of interface
Want more information about Forge?  You can sign up for our newsletter to receive product announcements or contact us to learn more.

Design a Molecule 4: Sneak Peek

The next Design a Molecule competition begins on March 15th, 2012 and we’re so excited about the next target, we’re giving you a little sneak peek.  Like the last competition, the theme is anti-malarial, but this time we’ve chosen to focus on on a broad spectrum protein target relevant to antibacterials, antifungals and various plasmodium-like human parasites.

The enoyl acyl carrier protein reductase (ENR/FABL/FABI) is involved in fatty acid biosynthesis in bacteria, specifically in the liver stage of plasmodium falciparum life-cycle (PfENR) and more generally in that of Toxoplasmodium Gondi (TgENR).

Triclosan which is a broad spectrum anti-bacterial used in various applications, such as antibacterial soaps and toothpaste, is well established as an inhibitor of ENR’s.  More recently Triclosan has been shown to inhibit the human parasitic forms of plasmodium (PfENR and TgENR) showing some efficacy in mice – although there is controversy over the precise mechanism and involvement of PfENR as the primary target.  A number of X-ray structures are available of ENRs and triclosan analogues (below).

Conversion of Triclosan into a drug has a number of associated challenges:

1. Efficacy – less active sub-optimal at PfENR relative to bacteria

2. Toxicity – poly chlorination is an issue

3. Solubility – too lipophilic logP X TpSA Y – although has to pass through multiple membranes to access target

4. Resistance –  an issue in bacteria

Recent examples of optimisation of Triclosan for Plasmodium ENR have appeared in the literature – some of which may also have potential against resistant bacteria, as in the figure below.

We have created an artificial 3D ligand construct by combining some of the desirable ligand complex examples from the PDB in order to address poly-chlorination issues. It should be noted that this is simply a ‘virtual ligand template’, representing accessible ligand –protein interface within PfENR, which we hypothesise to be useful for scoring potential designs against – and is not a known active.

The challenge in this competition is therefore to design a ligand that addresses the issues above as much as possible. The winning entry will have the highest score against this construct whilst having the lowest 2D similarity. The winner will also be judged on synthetic tractability and the extent to which the design addresses the issues described above (1-4).

Competition Details

The competition runs March 15th – April 20th and we’ll give you more detailed instructions along with the 3D molecule file when registration opens.  If you’re new to Design a Molecule, here’s how it works:

1. Register for the competition

2. We’ll give you a target molecule and free licenses to FieldAlign and FieldView

3. Design the very best molecule

4. Submit the molecule to us

5.  Win an iPad2 (Well, only if you really designed the very best molecule in the bunch)

Feel free to contact us with questions about our target selection, the competition or using Cresset software for molecule Design.

Update March 15: The competition is now open, register here and see the instructions here.

Cresset and Optibrium Announce Technology Collaboration

Cambridge and Welwyn Garden City, UK, (January 4th, 2012) – Innovative software and services provider Cresset, and  Optibrium, a provider of software solutions for drug discovery, today announce an agreement to collaborate on the development of next-generation platforms. The innovative companies will work together, combining unique approaches to help drug discovery projects quickly identify novel, potent compounds with a high chance of success downstream.

The collaboration will involve a two-way exchange of technologies: Optibrium’s ADME[1] models, currently provided as a plug-in module for its StarDrop™ software platform, will be made available to users of Cresset’s desktop applications. Similarly, Cresset’s FieldAlign™ software, which helps chemists understand the three-dimensional structure-activity-relationship of their chemistry in order to design active compounds, will be made available as an optional plug-in module for StarDrop, which helps project teams to confidently target compounds with a good balance of properties for their therapeutic objectives.

Achieving a combination of potency with appropriate ADME and safety properties is essential to the discovery of high quality drug candidates. Cresset’s molecular field technology provides unique insight into the biological activity, properties and interactions of molecules, which enables biologically meaningful comparisons that are not limited by two-dimensional structure.  Optibrium’s StarDrop platform helps to guide decisions on the design and selection of compounds by integrating in silico and experimentally measured properties using a unique multi-parameter optimisation approach, chemical space and Glowing Molecule™ visualisations and predictive modelling.

Dr. Matthew Segall, CEO of Optibrium, said, “We are very happy to be working with the team at Cresset. This collaboration furthers our aim to deliver leading edge in silico technologies directly to the desktop of all drug discovery scientists through StarDrop’s user friendly, interactive interface. The new FieldAlign module in StarDrop will bring a powerful 3D view of compound interactions that will complement StarDrop’s existing 2D QSAR models.”

Dr. Robert Scoffin, CEO of Cresset, added “This collaboration is an excellent opportunity for two companies to combine talents and technologies in order to offer a better product to our combined customers. This highlights the power of bringing together complementary technologies from leading-edge companies to better address problems in Drug Discovery.”

The technology shared under this collaboration will form new components in upcoming releases of Optibrium’s StarDrop and Cresset’s desktop applications. Full details of these exciting new developments will be announced soon.

For more information about StarDrop and Optibrium’s software solutions please visit Optibrium’s website, alternatively please call +44 (0) 1223 815 900 or email Optibrium.

For more information about Cresset’s software and service solutions please visit Cressest’s website, alternatively email Cresset.


[1] Absorption, Distribution, Metabolism and Elimination

Design a Molecule Competition Fall 2011: Winner Announced

This Fall’s ‘Design A Molecule Competition’ was Cresset’s third and the second to have an Anti-Malarial flavor.  Contestants were asked to  design a molecule which reconnected the fragments of a Farnesyl Transferase inhibitor from the PDB and to effectively replace the core of the ligand with a new framework.  The choice of ligand and target was made with some thought to balance the ease and likely interest in the task with relevance in the field, without getting drawn too deeply into drug the discovery process and its many, many issues.

The very entertaining storm which ensued illustrated perfectly the potentially embroiling diversity of opinion in the drug discovery arena.  Despite this and initial reservations about the difficulty of the challenge, Cresset was delighted with the response to the competition.  The resultant entry molecules were ranked relative to the original bioactive/bound conformer using Cresset’s ‘3D Molecular Field Similarity’ in FieldAlign and then judged on synthetic tractability and drug-likeness. Novelty was also factored into the ranking by imposing a 2D similarity penalty.

Cresset has no commercial interest in exploiting IP from its competitions and so with consent from contestants we are very happy to disclose the winning structures.

Winner: Congratulations to Peter Ertl of Novartis, the winner of a brand new tablet!

Peter’s design was very elegant, compact, with far less conformational flexibility and high field and shape match, relative to the starting inhibitor. Peter cleverly used the triazole replacement to capture the fields provided by both imidazole moieties in the reference. In the complex these are involved in metal ion and H-bond acceptor interactions from tryptophan/tyrosine.  The aryl ether moiety would provide a suitable chemical handle for driving selectivity specifically towards the malarial target.  Peter’s design is reasonably drug-like, with a  low mwt 400, logP 4.6, TPSA 80 and synthetically tractable.

A very close second place result goes to Albert Kooistra (PhD student in the division of Medicinal Chemistry of VU University Amsterdam).  Albert’s design was so near to winning that we have awarded him with a second prize: An Amazon Kindle.  Well done!

Albert took a more literal approach, maintaining all the original fragments, to produce high field and shape match, although invoked a higher 2D similarity penalty than Peter. Albert engineered a very nice imidazol-sulphonamide bioisostere which maintains H-bonding interactions to Arg in the complex. These interactions are not as well served as by Peter’s design.  Albert’s design is also reasonably drug-like mwt 477, logP 3.9, TPSA 98 but is arguably less synthetically tractable or amenable to further synthetic exploration.

Finally, in the image below, you can see the molecules in the context of protein.

There were several other very nice results worthy of an honourable mention:

Andy Knox (Trinity College Dublin), Brad Teegarden (Consultant), and Sandeep Sundriyal (Texas A&M Health Science Center) all submitted cyano indole and aza-indole starting points, which scored highly and had great tractability.  And finally, a very worthy mention for Matt Baumgartner (University of Pittsburgh) who submitted all of his results featuring single step syntheses, showing a commendable appreciation of the issue of cost of goods and synthetic tractability in the Malarial field.

Congratulations to all of our winners and thank you to the rest of our entrants.  We will run this competition again, please watch for details.

September Design a Molecule

Detailed steps on how to enter the design competiton are presented below. Or watch the video version.

  1. Enter the competition to get everything you need
  2. Download the zip file using the link in the email that you get sent
  3. Unzip the downloaded file and follow the instructions in the readme document
  4. Install FieldAlign and FieldView from the “Software” folder
  5. In the “Competition” folder Double click the left mouse button on the FieldAlign project: “START_HERE_Sep11.fpj” to open this file in FieldAlign.
  6. Note two 2d molecules present in the molecule table: the reference (yellow block background) and four disconnected fragments (query)
  7. Select the query molecule in the table with the left mouse button (should turn to a blue background).
  8. Right click and select “Edit a copy of the selected molecule” to open the Molecule editor.
  9. Hold LMB on background and move mouse to rotate view.
  10. Edit (add atom) by dragging and holding LMB from a fragment. Ctrl-Z will undo. Hold Ctrl will toggle selection mode. Delete will delete selected atoms.
  11. Repeat to connect the fragments and design the replacement core using whichever atoms you wish: Select from the left hand atom menu; double click on a bond to toggle bonding.
  12. Minimise core only: Using the selection tool highlight the core (cyan) click minimise.
  13. Once you are happy: Save to exit the editor.
  14. To align the new molecule query and calculate a similarlty score: Click process (calculate icon) in the top menu.
  15. Repeat the process to refine the design or start again from the fragments.
  16. Once you have a winning design, export the molecule: Select the molecule to export by left clicking on it in the table then use File menu -> Export -> Export selected molecule
  17. Save the molecule to an sdf file
  18. Upload the molecule to enter or send it to