Questions relating to which information/email belongs to which project, which specific solutions have particular importance and further more complex analyses of screening results at deeper levels of detail for active molecules are important. Thus detailed notes can now be saved within a LeadIT Project File to consolidate all information in one place to stimulate joint conclusions and knowledge generation. Comments can also be appended to virtual screening solutions to permit the sharing of thoughts between researchers based on a specific LeadIT solution which may in the future be proposed as a candidate active molecule for testing. Additionally, viewing a particular solution in a specific 3D orientation may also be vitally important for understanding and interpreting others findings. Therefore a screen capture facility is a simple click away to allow each researcher to portray the exact same specific 3D angle and perspective used previously for analysis. Such features provide a platform for a much more rapid insight into proposed conclusions of researchers working within a team. Sharing ideas and discussing hypotheses about noteworthy screening solutions permits teams of researchers to affirm and together establish significant findings.

PoseView incorporated in LeadIT, is another piece of added value. It allows users to visualize protein-ligand complexes in 2D on the atomistic level. PoseView automatically generates high-quality 2D structure-diagrams of protein-ligand complexes provided as 3D-input. The atomistic 2D depiction of a complex shows hydrogen bonds as dashed lines between the interaction partners on either side. Hydrophobic interactions are illustrated as smooth contour lines between the respective amino acids and the ligand. The ligand itself is drawn utilizing the 2Ddraw engine according to chemical drawing conventions. Within the context of LeadIT now docking solutions from FlexX can be visualized in 2D using PoseView and exported to a variety of graphics formats for automatic generation of publication-quality graphics. The 2D depictions permit researchers to swiftly scrutinize, identify and share how a ligand is interacting with a protein.

Another novel feature in LeadIT 1.2 is the 'Assistant' help which intuitively provides a resource for users to be guided through the correct procedure for performing their desired flavor of virtual screening. The 'Assistant' describes what must be 'done/clicked' to progress through the procedural steps required for successful screening. It may be thought of as an on-the-fly tutorial!

If any of this strikes you as interesting and in case of any questions or comments please do email us.

DrugScore-CSD may now be used for docking and scoring within FlexX (integrated in LeadIT, starting from Release 1.2). LeadIT-FlexX effortlessly and efficiently implements the use of pair potentials by means of a generic interface. A settings file containing the CSD potentials includes all the necessary parameters for FlexX-Docking to utilize DrugScore-CSD potentials for scoring. As always a very generic approach to integrating such data was undertaken. In the case of Drugscore the so-called pair-potential interface (check out 'PPI' in the FlexX User Guide) provides a generic platform for integration. Generally speaking the PPI reads lengthy tables of pairs of atom-types with a distance-dependent pair potential. Aside of the two types of DrugScore, it handles all sorts of pair potential data. Users may even derive their own pair-potentials and use them, e.g., as a custom-made scoring function.

Thanks to our collaborators in the Klebe-lab of the University of Marburg as well as the Cambridge Crystallographic Data Centre we can make this terrific scoring function available. Particularly we would like to thank Gerd Neudert who implemented the final touches to this version of the DrugScore function and in making sure that our integrated version performs as consistently as his stand-alone version. To obtain your copy of Drugscore-CSD you will need a username and password — enter your 2010 CSD subscriber Site Number as your username, and Confirmation Code (without the leading 'CC') as the password in order to download the package. The README-file within the package will guide user, if you do experience any problems using Drugscore-CSD in LeadIT, or have any questions about Drugscore-CSD, FlexX, or LeadIT, please contact our support.

BioSolveIT ships LeadIT with a toy sandbox indexed fragment set based on the DUD subset of ZINC. This is primarily designed to allow users to 'play' with all the functionality within LeadIT rather then perform scientific analyses!!! This keeps the initial installation package of LeadIT to a minimal size and users can use the software within minutes of downloading. Additionally, a much more comprehensive indexed fragment set was created from 3.27 million molecules of the ZINC 'Lead Like' subset. All compounds from this 'Lead Like' subset only had their unique Bemis-Murcko scaffolds taken into account during index creation. This second indexed fragment set is the recommended dataset to work with when performing scientific studies therefore we highly recommend its installation.

Furthermore, an indexed fragment set has also been created from the Cambridge Structural Database (CSD) using precise crystal structure data which forms the highest quality input fragment data for scaffold hopping and FBLD with LeadIT. This fragment set can also easily be downloaded with CSD subscription data (please see above, final paragraph of the DrugScore section). However, there are no limitations with LeadIT, creation of your own individual indexed fragment dataset is easily possible with ReCore's built-in shredding functionality. The procedure is very simple and may be followed in this month's tips and tricks section. Many companies have already created, manipulated and conformationally enumerated fragments to successfully create unique and personalized indices to search their in-house data. If you have any questions please do contact us, or if you fancy picking up a copy of our super playful tool LeadIT just grab a copy.

BioSolveIT will be holding a variety of different workshops in the future tailored to the specific events they are linked to. The first two workshops which kicked off the series of BioSolveIT workshops were the Chemoinformatics Summer School in Obernai, France 20-24^th June and an FBDD workshop held in conjunction with the 5^th Sheffield Chemoinformatics Conference in Sheffield, UK on 13^th July. These workshops were a great success with around 140 and 35 attendees, respectively.

The third workshop of the summer will be also held in the UK, at Oxford University. This event is within the context of a week long training event provided by eCheminfo, which brings many different people from industrial and academic organizations together to be taught how to perform drug discovery on real practical drug design problems. The event incorporates a session from BioSolveIT where our FBLD methods will be applied on various case studies for many popular drug design targets.

The fourth event is a specialist workshop tailored to medicinal chemists that may have no prior experience in using software for computer-aided drug design. The workshop is being hosted at the 21^st International Symposium on Medicinal Chemistry IFMC-ISMC conference in Brussels, Belgium on the 7^th September.

The fifth and probably not the last workshop is being held at FBLD 2010 in Philadelphia, USA on the 10^th October. This workshop will be split into two separate parts, the first in conjunction with the Chemical Computing Group highlighting the synergies between BioSolveIT software and CCG's Molecular Operating Environment (MOE^®) modeling suite. The second component will be solely focusing on BioSolveIT software relating specifically to our individual FBLD approaches. If you have any interest in any of these workshops please do contact us.

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.