The distinctly new approach in Hyde is the heavy penalization of unmet interactions: A hydrogen bond taken out of the solvent - and not having an ideal partner in the protein; or the phenyl ring that is dehydrated and put into a hydrophilic active site region. Thus, not by rewarding H-bonds but by penalizing unfavorable situations, false positives are effectively ruled out in an in silico screen.

A Hyde assessment provides the user with an estimated free energy of binding. Additionally, an intuitive color coding of the atoms reveals access points for molecular optimization: Red atoms convey unfavorable contributions to binding, green atoms correspond to favorable contributions. Thus, immediate remedy can be established by modifying the structure and re-assessing it.

Hyde aims at helping teams of MedChems and CompChems to decide which molecules to further pursue in a synthesis; also you could rank a series of compounds regarding their score. More application fields could be the refinement of crystal structures, or checking the effects of molecular variations on antibiotics resistances.

Of course, Hyde is streamlined into the LeadIT GUI and can be accessed through FlexX and ReCore, respectively by a mouse-click.

Have examples, pictures, and more on the Hyde website.

We now have KNIME^® nodes for the following scenarios:

	searching through compound libraries and Fragment Spaces with our fuzzy similarity engine FTrees
	docking with FlexX
	aligning molecules in 3D with FlexS.

This suite of tools is completed by a few auxiliary tools like a very comfortable interactive table that visualizes FTrees mappings and allows interactive sorting and filtering, a 3D viewer to browse through sets of FlexS alignments, and a really fast engine to convert standard molecular and graphic formats.

The 2D drawing engine which can also be used as renderer within KNIME^® is based on the latest 2D drawing technology from the Center for Bioinformatics in Hamburg (ZBH).

A final touch of usability rounds up the new generation of our KNIME^® nodes:
There are new, separate installation packages for all binaries that install all required software out of the box. The easy update mechanism that was introduced into KNIME^® with Version 2.3.0 is now supported. And finally, all functionality is also available on the KNIME^® cluster and integrates seamlessly into KNIME^®'s reporting facilities. These were the last preparative steps before the BioSolveIT KNIME^® nodes will soon get the certification stamp from KNIME^®. Please obtain more details from our KNIME^® website.

Carsten Detering talked about how the chemical universe can be conquered more efficiently by incorporating chemical synthesis into creating a giant combinatorial chemistry space. In this context, giant means traditionally intractable numbers of >10⁹ molecules. Without ever enumerating the fragments to compounds, FTrees-FS can search directly in the fragment space for compounds similar to one or more given queries. Find the talk here.

This possibility was also addressed in a talk co-authored by Warren Wade of BioBlocks and Christian Lemmen, CEO of BioSolveIT. "With this method, we can virtually search the Syntheverse. The user gets hits from an FTrees-FS search, and these hits can directly be synthesized according to BioBlocks' building blocks and reaction protocols", says Christian. "Everything possible from BioBlocks' pool of reactions is virtually accessible, and ultimately in reality as well." Even considering only two reactions, access is given to numbers of compounds in the millions. With the inclusion of more reactions, this number can easily be pushed into the billions or trillions. Please find the slides here.

Carsten gave a second talk about LeadIT/ReCore's ability to strengthen teams of MedChems and CompChems due to its interactivity and intuitive GUI design. Find out more about the software here; the talk can be downloaded here.

BioSolveIT participated again in the session "Challenges in Industrial Computational Methods". There was a wealth of interesting and stimulating talks, e.g. by Dominic Ryan, Terry Stouch, or Vijay Pande, followed by intensive discussions about various topics of scientific software applications in the industry and in academic institutions. In this session, Christian Lemmen talked further about the new Hyde ligand binding assessment: "Hyde: Scoring for lead optimization".

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