2024.06

The 2024.06 release of Chemical Computing Group's Molecular Operating Environment (MOE) software includes a variety of new features, enhancements and changes that are summarized in this document.

Core System

Updated EHT angle and torsion parameterization. A novel bond angle and torsion parameterization methodology based on percentage s hybridization on directional bonds is now used for all forcefield EHT calculations in MOE. The new parameters have been found to lead to good agreement with QM geometry predictions. Note: As a consequence, Amber10:EHT energy terms may differ from those in MOE 2022.02 and earlier.

NEW! AmberEHTo Forcefield. The new AmberEHTo forcefield is similar to the new AmberEHT forcefield, the difference being that it uses:

• EHT for bond lengths, angles, and out-of-plane parameters.
• OpenFF 2.1 (Sage) SMIRKS torsion parameters.

Note that the AMBER CMAP is now saved to PRMTOP files, to correct backbone torsion psi-phi angles in proteins during Amber MD simulations.

Potential Setup. A new Selected Atoms Only option on the Parameters tab of the Potential Setup panel allows for displaying the parameters of only the atoms currently selected in the system.

Updated pKa model. The pKa model in MOE was retrained and improved. Note: this may result in differences from MOE 2022; for example, in protomer enumeration.

NEW! Ligand Torsion Analyzer. MOE | RHS | Ligand | Ligand Torsions launches a monitor for dynamically assessing the quality of dihedral angles in the current system based on their consistency with CSD statistics. Bond sleeves with traffic light coloring are displayed in the MOE 3D window as quality indicators, along with a text summary. Additionally, a Ligand Torsion Analyzer color bar can be displayed in the MOE footer Dihedral Plot for the currently selected torsion.

NEW! OpenMOPAC integration. OpenMOPAC 22.1.1 is now distributed with MOE. MOPAC 7, which was previously distributed with MOE, is no longer part of the MOE distribution in 2024.

OpenMOPAC has been integrated into all applications in MOE that supported the use of MOPAC 7, 2012, or 2016. In particular, support for the MOZYME keyword has been explicitly added to the MOPAC settings page, provided as a Linear Scaling (MOZYME) checkbox.

NEW! Database Viewer Filters. Filter Database, available through either DBV | Edit | Filter or the button in the menu bar of the Database Viewer, provides a quick interactive way to filter database entries by property. The distributions of database field values are displayed as histograms or lists of categorical values, in which a range of values can be specified. The data display is updated dynamically when any changes are made to the database contents.

Filter Database provides the following:

• Up to 10 filters.
• Interactive filter adjustment.
• Visual cues to indicate which part of the data are included / excluded by the filtering process.
• Logical AND and OR combining operations.
• Filter inversion (logical NOT operator).
• Set entry selection or visibility based on filters.
• Enable / disable filters.
• Collapsed, summary view of filters.
• Choose whether to use first, minimum, maximum, or average of multi-value database cells.
• Choose whether to always filter out empty cells or cells with non-finite values.
• Attached and detached modes.

File formats. Support for the following file formats has been added or enhanced:

• The following file formats have been added to the Save panel (MOE | File | Save):
  • mmCIF
  • XYZ
  • MDB
• Multi-model PDB files can now be written from the Save panel.
• Saving biopolymers (proteins, nucleic acids) as sequences is now available when saving a database as a text or CSV file (DBV | File | Save As ).
• Reading of binary CIF files is now supported in the Open panel.
• The AMBER CMAP is now written to PRMTOP files.

Support for 5-letter residue names. PDB reading and writing has been updated to support round-trip preservation of 5-letter residue names in MOE. Long names are mapped to short names, with the mapping written into REMARK 99 for recovering the long names on reading. Reading and writing of REMARK 600 records containing long residue names is now supported as well.

Pi-pi contacts. The display of π-π interactions (between planar rings) can be enabled from the MOE Footer | Contacts popup.

Ribbon display. Ribbons have been updated with the following features:

• Smooth colors. Ribbon color can be interpolated between differently colored segments.
• Beveled edges. Ribbons displayed using cartoon rendering can be drawn with beveled edges to smooth out the corners.

System Manager. The System Manager context menu, opened by right clicking on any of the lines in the System Manager, now provides a Show 2D button that shows the corresponding molecule in the 2D overlay display in the MOE Window.

UI Zoom. The UI zoom factor of MOE windows can now be done on a per-monitor as well as a per-window basis:

• Per-monitor zoom. In a multi-monitor system, scaling of individual monitors can be specified in the Configuration Options panel. A schematic in the panel shows the available monitors and their arrangement in the operating system. When scaling to very large sizes, a confirmation dialog will open; if no confirmation is made, the zoom will be reverted after 15 seconds.
• Per-window zoom. Individual MOE windows can be dynamically zoomed using the following key combinations:
  • Zoom out (reduce zoom): Ctrl–, i.e. hold the Control key and press –.
  • Zoom in (increase zoom): Ctrl= (or Ctrl+), i.e. hold the Control key and press =.
  • Reset zoom: Ctrl0, i.e. hold the Control key and press 0 (zero).

Bubble Help. Bubble help in the Database Viewer and Sequence Editor have been enhanced as follows:

• Sequence Editor. The bubble help on non-natural amino acids will now show a 2D depiction of the residue.
• Database Viewer. A new set of Bubble Help buttons in the Database Viewer page of the Configuration Options panel are used to set the display mode of bubble help on minimized molecule cells; the bubble help can be always shown or always hidden, or shown only when a modifier is held down while hovering.

NEW! Video links. Context-sensitive video help is now available for many of the panels in MOE. In addition to the manual page link, where available, one or more video links will be listed when the help button is pressed. If no video links are available, the manual page will open automatically.

Selection expression language. The following updates have been made:

• Adding a '?' character suffix when specifying a set name will result in all objects being returned when the set is undefined; without the suffix, no objects are returned.
• The buried and exposed keywords now take a selection expression as an additional optional argument; when specified, the keywords will apply only to the objects defined by the expression.

Third party software support. The following software versions are now supported:

• Gaussian: g16RevC.01
• AMBER: AMBER 24
• CUDA SDK: CUDA 12

Note that precompiled GPU ptx files are now patchable; i.e. they can be added to the MOE patch and custom directories.

MOE menus. The following changes have been made to MOE menus.

Applications

Conformation Import. In 2024, Conformation Import was rewritten for better performance and reliability:

• Improved fragmentation rules now create fewer fragments with a better chemical context.
• Penalty functions are used to prevent the generation of unwanted conformations such as, for example, cis-amides.
• Fragment databases are much smaller than in the previous version; fragments were minimized using the new AmberEHT forcefield.
• The panel was streamlined and simplified.

As a consequence of these updates, there almost no failure cases (i.e. where conformations cannot be generated), and calculations are generally much faster than with the previous version.

Note: the output database is now always written with conformations in packed mode.

NEW! Capture. Capture provides the ability to easily save the current system along with a title and text annotations – together referred to as a capture – and subsequently browse and edit saved captures. Captures are saved to a Capture file which is specified when the application is launched, and which can be switched later in the MOE session if desired.

Features include:

• MOE | RHS | Capture provides quick access to Add (add a new capture to the Capture file) and Open (switch Capture files) options, as well as loading from a list of captures. MOE | File | Captures provides the same menu access.
• Attached and detached panel modes. In attached mode, Capture opens in the MOE Footer, with buttons for quick loading, Add, and Edit, and a list popup that includes search, reordering, and delete capability. In detached mode, Capture is launched as a separate panel. The default launch mode is configurable.
• Smooth transitions when loading a capture. The duration of the transition can be configured.
• Save options to specify whether to save only tags with active atoms or only the active ligand, surfaces, and the current theme (view setup). Note that if Ligand Properties are currently displayed, they will be captured too.
• On hover over the Capture footer buttons or Capture list items, bubble help will display a summary of the capture, including a thumbnail of the saved system.
• Traversal between Title and Comment fields using keyboard Tab key. (Use Shift-Tab to enter a text tab.)

MOEsaic. MOEsaic, the web-based application for Structure Activity Relationship (SAR) and Matched Molecular Pair (MMP) analysis, has been enhanced as follows:

• Improved Filtering. Filters were fully redesigned. Data distributions are shown as histograms for numerical fields, percentages for categorical fields, and depictions for structure fields. OR and AND combining logic and logical inversion are available.
• Heat Map. The new Heatmap Pane is used to pinpoint where there may be compounds of interest or not of interest in the fully enumerated combinations of an R-Group Analysis fragmentation. Features include:

  

  • Dynamic zoom. Using the zoom button in the UI or Ctrl + wheel, the display will zoom in or out. The fully zoomed-in view shows individual fragment and compound depictions. Zooming out loses detail, finally leading to an overview mode in which a sampled view of the data on a regular grid is shown.
  • Summary information in bubble help. On mouse hover over the tiles of the heat map display, bubble help will appear with a summary of the data corresponding to that tile.
  • Column and row sorting. By default, columns and rows in the display are sorted by the main activity field. Sorting by any field is possible through Sort options in the pane's header.
  • Calculate fragment activity using a model. A MOE QSAR model can be used to calculate the activity value of the fragments. If no model is specified, Free Wilson analysis is used to calculate the contribution of each fragment. Fragments can be colored and sorted based on their contribution.
• QSAR models. QSAR models are configured in MOEsaic in the new Qsar Models page of the Project Configuration panel.
  • Upload model files. MOE .fit files can be drag and dropped or selected via a file browser.
  • Create model from descriptors. A model can be created or modified manually by selecting descriptors from all available MOE descriptors and then adding them to the model.
• View Templates. The new View Templates pane in the Project Configuration panel allows for specifying custom layouts for each type of tab.
• New plot types. The Plot pane now offers radar plots, box bar plots, and bar charts. These plots are useful for comparing compounds to one another along different property dimensions.
• Custom hooks. Hooks provide a mechanism for quickly and easily sending requests from MOEsaic to third party servers.
• Interaction and pocket surfaces. The Dock pane now generates and displays interaction surfaces and pocket molecular surfaces colored by electrotstatics.

Protein structural alignment. The protein structural alignment methodology in MOE has been redesigned for greater accuracy.

• Pairwise protein alignment. The pairwise protein alignment algorithm optimizes the STOVCA alignment quality score, which is based on percentage of aligned alpha carbons.
• Multiple protein alignment. The new multiple alignment method searches for optimal pairwise constraints then builds up a global alignment from the pairwise alignments of each pair of structures using a tree build-up strategy.
• Stuctural Overlap. In SE | Align/Superpose, the new Structural Overlap button in the Superpose Options popup specifies that the superposition to be performed will correspond to the calculations used to optimize the protein alignment, i.e. which will maximize the number of equivalenced residues according to STOVCA criteria.
• Pairwise Overlap Scan. This new option in the Align Options popup, when disabled, will perform a faster, less thorough search; this may fail when sequence identity between sequences is low. Enable this option to perform the full search.

Pharmacophore Search with subsets. Pharmacophore Search now support the use of selection expressions for restricting the pharmacophore search to a subset of atoms of the system. This makes it possible, for example, to use pharmacophore search to quickly find protein-protein docking poses that satisfy particular interaction requirements.

The new Selection option provides the ability to restrict the search by specifying the following sets of atoms:

• Annotate. The atoms that will be annotated for feature matching.
• Bcheck. The atoms to use for a bump check on projected annotations
• Volumes. The atoms to consider during volume checks.
• Molecule. A set of atoms that will be used by default when any of the above sets is left unspecified.

Pharmacophore Query Volume Expressions. The Pharmacophore Editor now supports the use of selection expressions and sets in Volume expressions.

Spectral Analysis. The Spectral Analysis application has been enhanced with the following updates:

• ECD. Electronic Circular Dichroism (ECD) spectra are now available in a new tab. Analogously to the VCD tab where the complementary IR spectra could be displayed, the UV spectrum can be displayed next to the ECD spectrum.
• ORD. Optical rotation dispersion (ORD) is related to ECD via the Kramers-Kronig transformation. ORD spectra can be displayed on the ECD page.
• Conformer Distribution Fitting Weights. When multiple experimental properties are used for fitting, it is now possible to assign a greater or lesser weight to the Chemical Shifts and Coupling Constants contributions. This is useful when it is known that a particular property has greater or lesser accuracy.
• Conformer Distribution 2D display of errors. Similarly to the NMR tab 2D structure display, the Conformer Distribution 2D diagram now shows colored circles scaled by the error of each conformer.
• Duplicate removal RMSD limit. Each tab in the Spectral Analysis panel now provides a configurable RMSD threshold for duplicated removal.
• Averaged calculated shift for CH3. On the NMR tab, calculated H shifts are averaged for methyl groups.
• Save coupling constants. On the NMR tab, the table of coupling constants now offers a Save button.
• Conformer Distribution report. A Create Report button has been added to the Conformer Distribution tab.
• VCD Summary Report. An option has been added to create the VCD report in summary mode.
• Peak Half-Width. On both the VCD and ECD tabs, it is possible now to specify the peak half-width of the selected line shape. This is useful when experimental values might have a lower resolution than the calculated values. By broadening the peak, the theoretical calculation is effectively performed at a coarser resolution, thus potentially providing a better match to the experimental shape.
• Reset Zoom. This button has been added to the NMR, VCD, and ECD tabs.

Note: In Conformation Search, QM duplicate removal is no longer done.

QuickPrep. Overwrite Temperature Factor by Displacement is a new refinement option which, when enabled, overwrites the atom temperature factor with the distance the atom moved during minimization, multiplied by 30.0.

Protein Patches. Protein Patches 2D Maps has been enhanced as follows:

• Map Average. When patches belonging to multiple structures are present in the system, the averaged 2D patches can be displayed by selecting several structures from the list of maps.
• Map Difference. When Map Difference is enabled, the difference between specified maps or averaged maps is displayed.
• Show / Hide. When multiple maps as present, the maps can be displayed in single or double pane mode by showing or hiding one or the other of the map panes.
• Horizontal / Vertical alignment. When both map panes are visible, they can be oriented side-by-side or over-under using the new Horizontal Align setting.
• Legend. Each map pane now has an associated legend popup.
• MDB input. Input structures can now be read from a MOE database file (.mdb).
• Save settings. Panel configurations can be saved and restored.

The Protein Patch Analyzer has a new Area field that reports the cumulative total patch area of all patches listed.

Protein patches can now be calculated over a database. DBV | Compute | Molecule | Protein Patches opens the Save Protein Patches panel, in which the type of patch as well as patch parameters can be specified.

Ensemble Protein Properties. The following are new features in Protein Properties:

• Save patches in database. When enabled, an extra field will be written to the ensemble database containing the protein patches that are generated while calculating patch properties. Note that this may significantly increase the size of the file.
• Save surface. When enabled, an extra field will be written to the ensemble database containing the molecular surfaces of the input structures, colored by a specified ensemble average residue property. The coloring scheme can be configured.
• Subset support. When calculating properties on a database of structures, it is now possible to specify a subset of the system over which to perform calculations, including named sets.
• Environment Charge. The net charge of the fixed (not sampled) part of the system can now be specified. This value is added to the sampled charge for determining the pI of the combined system.

Epitope Analyzer. When browsing a database that contains computed epitopes, the epitope analysis panel is now embedded in the DBV Browser.

Protein Design. Two new options have been added to Protein Design:

• Preserve Restraints. Tethers, forcefield restraints, and atom fixed state are used to determine whether a residue will be included or excluded from sidechain repacking. This can be used to enforce specific conformations.
• Lower Site Limit. It is now possible to specify the lower limit of Site Limit enumeration.
• Load Mutation Sequence. A sequence file in FastA or raw format can be specified to define the list of mutations.

Protein Contacts. Protein Contacts provides new PosA and PosB aggregation modes. These allow summarizing all interactions for a unique residue in SetA or SetB, respectively. Since multiple residue contacts and types may exist, the corresponding interacting pair in PosB or PosA, respectively, may be a list of residue names/positions.

Pro:Pro Dock. When the system contains an annotated antibody-antigen complex, Protein-Protein Docking will now auto-select the antibody as the ligand, and the antigen as the receptor. $CDR_H3 is then auto-selected as the ligand site (the active site on the ligand), and Use Hydrophobic Patch Potential is enabled by default. "Antibody mode" is enabled through a single Auto-detect CDR Site Restraints option, which automatically detects antibody structures and, if found, automatically uses the CDR H3 loop as an additional site restraint.

In batch mode, a Verbose Log File can now be specified. Extra progress information is written to this file during the docking run.

Antibody Modeler. The Antibody Modeler has the following enhancements:

• Refinement. A new refinement protocol is now used to generate the final model. In a slow-quenching approach, heavy atoms are restrained and minimized iteratively, which can help improve the stability of the results.

  

• Cleave terminal Lysines. When building a full Ig model, the Full Ig Termini option, when enabled, will result in C-terminal Lysine residues being removed prior to adding terminal caps. This option is available only when Model Type is set to Ig.

MOE project database RNA support. Support for RNA families has been added to the following applications in MOE:

• Project Search. Sequence search, substructure search, and general RNA residue handling is now supported in the Project Search panel. Note that remote PSILO families can now be included in Project Search; this is configured from the MOE Configuration Options panel and requires a valid PSILO server to be specified.
• Project building. MOE RNA projects can now be built using Protein Database Update. RFAM codes are supported, with RCSB as the source.

Database Wash. The Database Wash application has been enhanced with a Entropic Filtering option which, when enabled, will result in protomers with insignificant contributions being removed. This option is only available when the Protonation mode is set to Enumerate.

Database Wash now also provides a Batch button which can be used to submit Wash jobs to a queueing system, or to perform local calculations at a later time. The application has also been reimplemented to support MPU parallelization.

Database Correlation. A new Clipboard button in the Database Correlation panel copies the correlation matrix R values and field titles onto the text clipboard in tab-separated form.

Descriptors. The following descriptors have been added:

Fragment tools. Several new options have been added to the fragment tools:

• Dominant Protomer. In Scaffold Replacement, Link Multiple Fragments, and Add Group to Ligand, when this option is enabled, the dominant protomer of the generated structure will be output. The result can be output as a 2D depiction, 3D ligand structure, or 3D structure of both the ligand and pocket.
• Create Double Bonds. In Scaffold Replacement, Link Multiple Fragments, and Add Group to Ligand, when this option is enabled, both single and double bonds will be created when making connections, where permitted by geometry and molecular topology.
• Maintain Score. Available in all fragment tools, this option when enabled filters results so that only hits with improved ligand/receptor scores will be retained. Original will output all structures with scores lower than that of the original complex, whereas Maximum will output only structures whose score is better than that of all structures already output up to that point.
• Topologically Unique. This option, already available in several other fragment tools, has now been added to Combinatorial Builder. When enabled, only hits that are topologically unique from all other results up to that point are output.

AMBER TI. A dt option has been added to AMBER TI; reduction of dt can help mitigate AMBER calculation instability. The range of values is limited to what is reasonable for the simulations.

Solvate. The following updates have been made to Solvate.

• Shape. Two new shapes have been added in Periodic mode: Trunc. Oct. generates images for space group I1 (two images per box) in the shape of a truncated octahedron, and Rh. Dodec. for F1 (four images per box), in the shape of a rhombic dodecahedron.
• Minimize. When enabled, minimization of the atoms in the primitive cell is performed, taking into account lattice symmetry. This can help remove clashes due to non-orthogonal image boundaries with non-primitive unit cells.
• Show Box. For non-primitive periodic cells (e.g. Trunc. Oct. or Rh. Dodec.), display the outline of the of the asymmetric box centered in the periodic cell. Note that this graphic can be toggled on or off using the new Hide Graphics button in the Crystal Parameters panel (the button is available only when a non-primitive periodic cell is in effect).

Flexible Alignment. A new Planar Systems are Rigid Bodies option, when enabled, will enforce that all π systems (connected components consisting of atoms connected with bonds of high π bond order), will be treated as rigid bodies.

Data Files

$MOE/lib files. The following changes have been made to $MOE/lib:

Sample molecular data files. The following changes have been made to $MOE/sample/mol, the directory of sample molecular data files:

SVL Programming

The following are SVL functions that have been added to or modified in MOE. Please consult the SVL Function Index for more information.

    mdl_ParseCTAB [lines, qflag]

    mdl_ParseCTAB [lines, [query:qflag, hcount:0]]

    smi = sm_ExtractUnique sm_BuildParse smi;

Widgets. The following attributes have been added to widgets that compose panels.

The following are SVL functions that have been deprecated or removed from MOE. In brief, all MOPAC 7.0 functions have been removed.

Platforms

Windows

The following platforms have been deprecated.

• Windows 7, 8, and 8.1.

Supported Windows platforms are 10 and 11.

Linux

Please note that OpenMOPAC requires glibc 2.14 to run. It is also anticipated that in upcoming releases, the minimum requirement for MOE will also be glibc 2.14, which would imply a minimum requirement of the following platforms:

• RHEL/CentOS 7
• Ubuntu: 12.04 LTS precise
• Debian: 8.0 jessie
• Fedora: 16 verne
• OpenSUS Linux EnterpriseE: 12.1

and the deprecation of the following platforms in upcoming releases:

• RHEL/CentOS 6 and earlier
• Ubuntu: 8.04 LTS hardy and earlier
• Debian: 5.0 lenny and earlier
• Fedora: 8 werewolf and earlier
• OpenSUS Linux EnterpriseE: 11.0 and earlier

These are supported in the current release, but official support may be discontinued in the next release.

Java Version

Note that the minimum Java version required to run MOE is Java 8.

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