Given a user-defined central unit of a molecule, the core, the best possible replacement — whilst keeping all connected atoms, i.e., the side chains in place — is identified from a 3D fragment database of possible moieties. Solutions can be influenced interactively by defining priority constraints, such as H-bond acceptor/donor interactions in a particular vicinity etc., these constraints act like pharmacophores. A typical workflow is a two stage process shown in the diagram to the left (click to enlarge), of which Stage A needs to be performed only once.

Infinite replacement scaffold moieties are obtained by shredding drug-like molecules in 3D molecular libraries to obtain maximum success and synthesizability. A graphical user interface for ReCore (pictured) will be released in the New Year whilst a command line version is available now. You can view a tutorial movie and also have the possibility of using this interesting unique tool with a free evaluation.

Standard FTrees provides much more than just a typical similarity score. Due to FTrees' powerful scaffold hopping capabilities solutions sometimes may appear to be unrelated, however unlike many other ligand based tools FTrees provides an alignment of ligands within Feature Trees descriptor space by retaining molecular topology. These alignments are one click away with FTreesXL and are effortlessly visualized. Such alignments provide a sound physiochemical basis why an FTrees hit is classified as highly similar to a query molecule and a sound rational approach for reasoning with medicinal chemists.

The GUI also contains data analysis capabilities as tabulated solution scores can be sorted and filtered in various ways to narrow down hit lists and may be exported for further processing. Whilst utilizing a variety of different clustering algorithms permits classification and identification of different chemical classes of molecules within screening sets. FTreesXL is currently in beta-testing and is available for users to evaluate on the Linux platform, please contact us.

The FlexX-GUI can be utilized to undertake highly detailed protein preparation and parameter adjustment. Subsequently the entire setup may be exported from the GUI and imported into Pipeline Pilot with a simplistic drag and drop. A ready-to-use Pipeline Pilot interface for FTrees can be downloaded from our web-page.

This first release of Pipeline Pilot interfaces consist of modules for remote and server computing as well as viewer components adapted specifically for visualizing results from BioSolveIT software. The modules facilitate virtual screening of compound libraries and the remote-computation module utilizes PVM to permit parallel computing on clusters. For further details on how to plug in and empower please do contact us.

BioSolveIT also recently presented a practical workshop on the FlexX GUI at the Drug Design Summer School held in Vienna, Austria. Over 60 participants were tutored during two different sessions on how to use the new FlexX GUI to perform successful protein-ligand docking.

You can view previous topics of tips and tricks here. If you have any questions or know of any tips and tricks yourself that you would like to share with the FlexX user community, we would appreciate your input at FlexX-info@BioSolveIT.de.