We are delighted to announce the release of a new version of Spark, our innovative tool for finding biologically equivalent replacements for key moieties in your molecule. This release contains many new features and improvements to the user interface along with new databases of bioisosteric fragments and hence is highly recommended for all users. Two key focuses for this version have been to improve the link between suggested bioisosteres and the available synthetic and property space of your project, and to make ranking Spark’s suggestions on multiple physicochemical properties easier and more intuitive.
The new radial plots summarize the properties of Spark result molecules in an instantly readable and interpretable way. These totally customizable and sortable additions to the molecule table enable the rapid visual profiling of new bioisosteres against personal, project or corporate physicochemical properties. Setting up the plots is easy – just pick the property to be added to the plot from a drop down list. The settings for ‘good’ and ‘acceptable’ values are easily customizable so that you can create a corporate or project based profile that can be used in every Spark experiment. Sorting on the radial plot column causes the result molecules with the best overall properties to rise to the top of the table, reducing the time taken to choose the best possible synthetic direction for your project.
The new ‘field difference’ display mode enables greater understanding of the effect of a specific change on the electrostatic and shape properties of your molecule. In this mode the regions of change in field of the result molecule are highlighted next to the starting molecule. Thus regions that become more positive or negative are easily spotted giving greater understanding of the differing shape and electrostatic characteristics of a change.
New in this version of Spark are databases of fragments derived from chemical reagents and building blocks. These new databases enable the use of Spark to scan the immediately available chemical space for the best possible move. The databases come from the processing of sets of commercially-available reagents with simple, chemically intuitive rules for generation of R groups. Over 20 different reagent databases are provided by Cresset using the current rules,which can be easily modified to suit your preferences. If you think we’ve missed something then let us know and we can add it to the list in minutes.
Customers with a database generator license can use our rules to process their own available reagents, giving rapid suggestions for the next set of compounds to be made using the reagents currently in your lab. Often these suggestions will warrant further investigation in Torch or Forge and so we have enhanced the link to these applications from Spark with a new “Send to” menu entry that transfers results to the chosen application.
Lastly we’ve introduced the option to create databases by fragmenting molecules that exist in a predefined conformation, such as those from small molecule crystal structures. We will be investigating the delivery of Cresset calculated databases from these sources in the next few months. However, customers with the database generator can use this mode immediately on their own or public crystal structures to further enhance their sources of bioisosteres.
This release of Spark is a significant advance: existing users will see great benefits from updating, while if you’re not already a Spark user contact us for a free evaluation to see what you’re missing out on!