News: Update: DivCon Discovery Suite 6.0.8 (build 22xx)

QuantumBio has released an update to DivCon6. This new version adds some key features to the software and addresses requests of current users. If you would like to explore the use of the software in your own structure based drug discovery efforts, contact sales@quantumbioinc.com or visit our licensing page.

Release Notes:

DivCon6.0.8 Build-22xx – August 5, 2014

  • New Feature. Symmetry is now supported on all full-QM methods including structure minimization, interaction energy and single point energy determination, and refinement using the ‘–symmetry’ option.
  • New Feature. The user can choose to optimize a specific region within the macromolecular structure while computing the qm for the whole system. This functionality is fully compatible with the –symmetry option (e.g. –opt –ligand-selection //HEM///,//NCT/// –region 5 –symmetry).
  • Alpha Feature. The ONIOM, mixed-QM/MM method has been added to the suite and is now in the alpha stage. ONIOM combines the company’s semiempirical quantum mechanics and AMBER forcefield (94/99/10/12/13) implementations into a single energy framework. This early release supports single point energy and interaction energy calculations along with structure optimization. Atom typing, exotic species (metal, ligand, unknown amino acids, etcetera) determination, and region expansion are all fully automated and accessible on the command line using the ‘-h pm6 amberffXX’ option where XX may be 94, 99, 10, 12, and 13.
  • Fix. Steps within geometry optimizations performed with Divide and Conquer are now updated appropriately regarding neighborhood selections. This fixes the “The Following neighbor pairs should exist. Density inconsistencies will arise.” Exception during optimization runs.
  • Fix. Mulliken atomic charges are computed correctly now when –selection is used.
  • New Feature. Pairwise Energy Decomposition is now reported per residue interaction. A total is also reported regarding the ligand and all other residues (if a ligand is provided).
  • Performance Optimization: Improved efficiency of 1 center and 2 center electron integrals.
  • Fix. Collisions are no longer exceptions leading to greater robustness. Attempts to run and continue for optimization and other flows where a really close collision just produces a high energy step.
  • Fix. Improved algorithm for the detection of unprotonated residues to reduce the possibility of false stops.
  • Xray Refinement (Phenix/Divcon): Mulliken charges for the ligand that defines the selection is printed in the Phenix remark section of the output PDB file.
  • Xray Refinement (Phenix/Divcon): new keyword ‘qblib_ligand_selection’ that allows a user to specify the ligand for the Mulliken charge or PWD outputs.
  • Xray Refinement (qbphenix): new keyword ‘–jobID’ that simplifies the input. e.g. ‘–jobID name’ is equivalent to ‘ –pdbFile name.pdb –sfFile name.mtz –cifFile name.cif’ arguments.
  • Xray Refinement (qbphenix): new keyword ‘–dir’ that allows to run the Phenix job in the specified subdirectory.
  • Xray Refinement (qbphenix): new feature. if the selection is not provided then the ligand name(s) is picked up from the external CIF (if given) to define the QM region automatically.

DivCon6.0.7 Build-2067 – May 15, 2014

  • Updated the reference for Phenix/DivCon (Acta Cryst. 2014, D70, pp 1233-1247). This reference is printed in the PDB REMARK section. The PDF for this reference is available here: http://www.quantumbioinc.com/publications/show/10.1107-S1399004714002260
  • Bug fix: updated MOE:Protonate3D in order to address a problem where truncated residues (with a single atom) would be “flipped” causing cases where residues would have multiple heavy atoms with the same name. This fix requires MOE2013.
  • Fix: occasional MOE-induced duplicate hydrogen names.
  • Improved transition metal charge assignment to better guarantee closed shell calculation.
  • Improved the mechanism for detection of non-zero spin states on atoms that are not currently supported by Phenix/DivCon.
  • Improved error reporting in phenix.log file.
  • Added a warning message if an atom makes extra bonds.
  • WebPage: Evaluation Planning page has been added to the online manual. See: http://www.quantumbioinc.com/support/manual-phenixdc/evaluation
  • Bug fix: Addressed a problem that can result in incorrect selection processing in Phenix/DivCon, interaction energy decomposition, etc. This problem was more prevalent when wildcard ’s were used (e.g. –selection “//115/*//”) or in cases where the ligand name was numeric.
  • Updated memory calculation for both “standard” and divide and conquer calculations.
  • Improved matrix management in the H5 file. Molecular orbital matrices were being stored to the H5 file even if enough memory was requested.
  • New feature: –fix-open-shell [noopt] switch in the event that a bond is “left open” due to a missing atom (such as in truncation or other issues). This switch will fix this problem through the addition of a proton. If arg=”opt”, the method will optimize any added protons.

DivCon6.0.6 Build-2002 – April 17, 2014

  • Bug Fix: During further testing of build-1997, a problem was detected in certain types of structures during interaction energy and decomposition calculations. This version fixes this problem and the method should be applicable to most structures. Since there are particular users that require this functionality, we felt that a quick follow up with this fix was in order.
  • Performance Enhancement: DivCon6.0.6 includes a key performance enhancement that can make Phenix/DivCon calculations much faster (potentially 1.5x or more depending upon the size of the QM region).

DivCon6.0.5 Build-1997 – April 15, 2014

  • Correct treatment of false atom radicalization due to pre-refinement structural inconsistencies, “hot spots” and other issues. This problem had lead to complaints of “odd number of electrons” in previous versions even when the chemistry was correct.
  • Acceptance of non-integer values for memory options in MOE/DivCon and Phenix/DivCon. In prior versions, the user would need to make sure that the memory value was a whole number.
  • More accurate memory prediction both in Phenix/DivCon and in SVL. This information is also provided as part of the screen output during the calculation.
  • Additional phenix.log warnings and information concerning memory requirements for optimal performance. If there is less memory available than optimal, the simulation will still proceed – albeit at a slower pace.
  • Updated SVL for better preparation (along with new documentation of the same to be posted on http://www.quantumbioinc.com/products/phenix_divcon tutorials and case studies).
  • Updated csh environment scripts. In previous versions, using the csh script would lead to spurious object file linking of non-QuantumBio software. Note: due to limitations in CSH/TCSH, the location of $QBHOME is fixed at installation and this qbenv.csh file will need to be updated in the event that $QBHOME is moved.
  • Updated moe-menus file to remove outdated or obsolete functionality.
  • BETA: Updated symmetry calculation for additional space groups available in non-regional/full refinement. For examples and information, contact support@quantumbioinc.com
  • BETA: Interaction energy calculation and decomposition (e.g. Eint, Epol, Ees, and Ect) available on qmechanic command line. In the coming weeks, documentation and examples will be provided at http://www.quantumbioinc.com/products/scoring

DivCon6.0.4 Build-1947 – March 27, 2014

  • Bug Fix: In previous versions, the gradients for protons remained unused in the refinement leading to poor proton refinement.
  • PDB File Support: Improved PDB parsing for unusual atom names.
  • PDB File Support: Added processing for HELIX and CRYST1.
  • Added the –repo option to qbphenix command line to allow for internal pdb/mtz repository.
  • New script and PBS template to be used as an example in running a large set of PDB structures.
  • Added qbLigandInteractions.svl file for MOE interface in order to generate ligand interactions diagrams (and analyses) automatically for pre- vs. post- refinement structures.
  • NEW Functionality (BETA): Symmetry has been added optionally when running full structure QM refinement (not available on regional refinement).

DivCon6.0.3 Build-1867

  • Improved error trapping for Phenix/DivCon including more accurate treatment of errors within the QM-region.
  • General maintenance release primarily consisting of “under the hood” performance improvements.

DivCon6.0.2 Build-1828

  • NEW for DivCon6 (!!): Updated pairwise energy decomposition (QM-PWD) command line-based functions – MOE interface coming soon!
  • NEW for DivCon6 (!!): Semiempirical QM-based nuclear magnetic resonance (QM-NMR) command line – MOE interface coming soon!
  • Overhauled thread system in order to maximize performance in multi-core environments.
  • Overall performance improvements.
  • Updated Phenix log feedback during refinement.
  • Completely updated Phenix/DivCon tutorials!

DivCon6.0.1 Build-1752

  • Bug fix: addresses occasional/intermittent segfault associated with specific types of ligands in refinement.
  • Bug fix: addresses segfault when calculating ligand strain on a single metal ion.
  • Updated phenix.log output to provide additional information about the core QM region along with the buffer QM region.
  • Increased speed and parallelism associated with the calculation of QM gradients.
  • Assorted perception and protonation fixes.
  • QBReporter improvements to process the h5 file and output the PWD, charges, and PDB geometries.

DivCon6

  • Complete overhaul of DivCon package using modern, high-performance design.
  • Pervasive, thread-based parallelism applied throughout the software.
  • Vastly improved SCF convergence both for linear scaling and for non-linear scaling techniques.
  • Implementation of AM1 and PM6 Hamiltonians for energy, PWD, and X-ray refinement.
  • Advanced nuclear magnetic resonance (NMR) capabilities for calculation of chemical shift and chemical shift perturbations.
  • Shipping integrations for both MOE (for NMR and modeling) and Phenix (for X-ray).