Scaffold activity diagram

Understanding structure activity relationship (SAR) is fundamental to early stage drug discovery.  With limited resources, the fate of a therapeutics campaign often rests upon the project team's ability to rationalize the SAR of a few selected chemotypes during hit-to-lead and/or lead-optimization.  Here R-group tables have predominately been used as communication devices throughout the decision making process.  Although very effective, R-group tables can quickly become unwieldy to manage for even a reasonable sized dataset.  Recently, a number of visualization tools (e.g., Scaffold Hunter and Scaffold Explorer just to name a couple) were introduced to complement the limitations of R-group tables.  These are highly interactive tools that---using advanced visualization techniques to display activity data---allow the user to quickly navigate the SAR landscape. In similar spirit, we recently put together a quick prototype for scaffold visualization.  Here we use graph layout instead of the typical tree hierarchy to organize the scaffolds.  The prototype is flexible in that it will initially discover all "relevant" scaffolds for a dataset.  Once the scaffold graph is generated, the user can edit (hide or add) the scaffolds at will.  There is no restrictions on the user-defined scaffolds; Markush scaffolds are fully supported, though it's recommended that the scaffold be properly aromatized prior to defining the query atoms.  Below are a few snapshots of the tool.  It comes bundled with a number of example datasets, so feel free to give it a try. The navigation controls are as follows.  Panning is performed through the standard mouse drag.  Zooming is achieved via (i) right-click and move up/down for a three-button mouse, or (ii) hold down the Command key and mouse button while moving up/down on the Mac. We would like to take this opportunity to make a few remarks about the tools available here.  First, we've gone the extra miles to make sure the tools run within the Java webstart sandbox.  What this means is that the tools run under a very restricted environment, so it's not possible for them to do harm to your computer without your explicit knowledge.  Secondly, the only network  communication that occurs between the tools and our server is to check for updates.  This is part of the Java webstart launching protocol and is not  something we have control over.  And lastly, we use Java 1.5 as the lowest  common denominator so as to support as many platforms as possible.  If you get a security warning about this from your operating system, you can safely ignore it.  We hope these measures are enough to convince you that you can  safely try the tools on proprietary data without reservations.

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