Today, we release version 7.5.0 of our flagship product: the DivCon Discovery Suite.
v7.5.0 is focused on improvements and continued maturity of our QM/MM-based crystallographic refinement and analysis tools including XModeScore and Phenix/DivCon. We have added several new features and improvements including integrated crystallographic protonation and tautomer/protomer characterization, a ~14+ fold speedup in CPU time for QM/MM calculations, expanded parallelism with PBS and SGE integration, and integrated density-driven docking (using MOE) for scoring fragment/ligand binding modes. We have also added a completely new tool for crystallographic “water picking” using a combination of Phenix/DivCon with MOE:3DRISM.
For more information about each of these applications and technologies, you are encouraged to review the following documentation:
- Updated Usage Planning Guide: If you are a new user (or if you would like to get up to speed on how the software is used), please review our updated Evaluation Planning Guide and Frequently Asked Questions pages for more information.
- Application: Fragment Based Drug Design: Phenix/DivCon coupled with the XModeScore tool has been applied to several key areas including protomer/tautomer determination, binding mode selection, crystal water positioning, and now even fragment-based screening. We have provided a tutorial of MOE-based fragment docking coupled with XModeScore-based selection.
- ONIOM (QM/MM) X-ray Refinement Standard: Last year we began a “beta” release of our fully automated QM/MM (ONIOM) implementation for X-ray refinement. Version 7.5 represents a complete overhaul for improved stability, and much greater performance (~14+ fold) and usability. ONIOM has now come out of “beta” status, and its use is shown in this example.
- New Structure/Chemistry Analyses: We have now packaged several before/after analyses within refinement including Clash Scores (using phenix.molprobity); Strain, Interaction Energies, and ZDD (using DivCon); and GBVI/WSA dG binding score prediction (using MOE – as available).
- Additional XModeScore Tutorials: Since our Version 7.0 release last year, XModeScore, our patent pending, crystallographic-based scoring method is used to experimentally determine binding modes, protonation and tautomer states, and crystallographic water locations. Additional tutorials can be found here. In particular, if you would like to use the PBS/SGE version of XModeScore, you should review this tutorial in order to modify the software to fit your environment.
- Protonation: Our “in house” protonation tool continues to evolve and mature, and it is now fully integrated with XModeScore and Phenix/DivCon. It includes a fast, integrated protonation and hydrogen bond network optimization method which uses a combination of dead end elimination and graph theory along with crystallographic symmetry and density – as available – to quickly and accurately determine the correct protonation states of bound ligands, active sites, waters, and protein/DNA/RNA.
- 3DRISM-based Crystallographic Water Picking: Determining the location of crystallographic water molecules is often a difficult, error prone process. This tool addresses this problem through the use of 3DRISM to help “filter” the density and determine which explicit waters fit both the crystallographic density and the prediction.
- Attention Computer Aided Drug Discovery (CADD) early adopters: Version 7.5.0 also includes a beta version of our fast, free-energy method based on the MovableType approach. This tool – including MTScore and MTConfSearch – will be available for industrial evaluation very soon! If you are interested in evaluating this method as it comes online, please take a look at our evaluation license agreement and Contact Us for more information.
Current clients have already received download instructions. If you would like to try the software or if you have any questions about the methods employed, please contact firstname.lastname@example.org and someone will get back to you right away.