| Interface | GUI | CLI |
| Ribbon menu structure for quick identification of commands and controls | | |
| Customize the display of tabs and function buttons in the ribbon menu using the Flare profiles | ✓ | |
| Launch multiple jobs locally or remotely | ✓ | ✓ |
| Monitor all running, queued, finished and cancelled jobs | ✓ | |
| Summary and detailed logging of calculations and events | ✓ | ✓ |
| Visualize protein-ligand interactions and steric clashes | ✓ | |
| Easily compare protein-ligand complexes | ✓ | |
| Grid the 3D window by protein and ligand to compare and contrast | ✓ | |
| Capture 3D view to the storyboard to track and communicate ideas | ✓ | |
| Create stunning high definition pictures for communication of results | ✓ | |
| Create informative videos of the 3D view and of the Flare GUI | ✓ | |
| Create interactive multi-series scatter plots boxplots and histograms of biological or physical properties | ✓ | |
| System (ligand and protein) preparation |
| Dedicated protein table enabling rapid inspection of specific chains or residues | ✓ | |
| Protein sequence alignment and superposition | ✓ | ✓ |
| Control every protein surface with individual display options in the dedicated protein surfaces table | ✓ | |
| Load and view electron density maps | ✓ | |
| Monitor alternate conformations for ligands and protein residues | ✓ | |
| Check protein structures for potential problems | ✓ | ✓ |
| Calculate and color protein molecular surfaces by secondary structure and hydrophobicity | ✓ | ✓ |
| Prepare proteins for further calculation | ✓ | ✓ |
| Perform single point mutation for your proteins | ✓ | ✓ |
| Protein minimization | ✓ | ✓ |
| Dedicated ligand table to store all ligands in your project with full visibility control, sortable on any column | ✓ | |
| Design ligands in the active site of the protein | ✓ | |
| Prepare ligands for further calculation | ✓ | |
| Calculated physico-chemical properties for each ligand | ✓ | ✓ |
| Calculate radial plot multi-parametric scores to select the compounds with the best properties | ✓ | ✓ |
| Filter ligands on physico-chemical properties, structures and tags | ✓ | |
| Visualize ligand electrostatics to gain a deep understanding of SAR | ✓ | |
| Minimize one or more ligands in the protein active site | ✓ | ✓ |
| Perform a geometry check of ligand torsions using the Mogul Library from CCDC (requires a CSD license) | ✓ | |
| Easy and accurate docking of ligands using 1 CPU core including ensemble, template and covalent docking methods | ✓ | ✓ |
| Constrain docking experiments to ensure specific pharmacophoric features are always matched | ✓ | ✓ |
| Dock ligands using multiple CPU cores including ensemble, template and covalent docking methods | Add-on | Add-on |
| Use HPC resources to rapidly dock thousands of ligands | Add-on | Add-on |
| Spark experiments |
| Search for novel cores for your molecules | ✓ | ✓ |
| Search for new R-groups based on the chemistry and reagents with up-to-date availability information | ✓ | ✓ |
| Grow a starter molecule into new regions of the active site mapped by another ligand | ✓ | ✓ |
| Join two ligands sitting in the same active site with a linker | ✓ | ✓ |
| Cyclize a molecule by joining two atoms with a linker | ✓ | ✓ |
| Search for a replacement group which will displace a crystallographic water molecule near your ligand | ✓ | ✓ |
| Find result molecules picking protein-ligand interactions not mapped by an existing starter or reference ligand | ✓ | ✓ |
| Grow a starter molecule into inoccupied pockets of the active site | ✓ | ✓ |
| Finding bioisosteres |
| Start from a 2D molecule | ✓ | ✓ |
| Start from a 3D conformation | ✓ | ✓ |
| Paste a starter molecule from ChemDraw or other applications | ✓ | |
| Download a starter molecule directly from the RCSB | ✓ | |
| Control the allowed elements and hybridization of atoms in all new bonds | ✓ | ✓ |
| Search one database at a time, inspecting results between runs, appending new results to an existing project | ✓ | ✓ |
| Search multiple databases in one process by selecting which databases to search at job initiation | ✓ | ✓ |
| Use field, pharmacophore and docking constraints to ensure specific interactions are maintained | ✓ | |
| Score results against multiple reference molecules | ✓ | ✓ |
| Score results using alternative similarity metrics | ✓ | ✓ |
| Score results by docking score using 1 CPU core | ✓ | ✓ |
| Filter on structure at calculation time using SMARTS patterns or fragments drawn with the molecular editor | ✓ | ✓ |
| Filter result molecules at calculation time according to the desired lipophilicity, polar surface area and flexibility profile | ✓ | ✓ |
| Filter result molecules at calculation time according to the desired size criteria | ✓ | ✓ |
| Import or export customized process settings | ✓ | ✓ |
| Connect to Cresset Engine Broker from Windows, Linux or Mac to use cloud and/or cluster resources for calculations | Add-on | Add-on |
| Viewing results | | |
| Browse 2D depictions of result molecules | ✓ | |
| Get every result molecule in 3D aligned to the starting molecule | ✓ | ✓ |
| View starter and results molecules and the protein in stereo | ✓ | |
| View protein ribbons in different styles | ✓ | |
| Limit protein to active site with simple button | ✓ | |
| View protein ribbons for the active site only | ✓ | |
| Use the Storyboard to capture, annotate, record and recall scenes from the 3D window | ✓ | |
| Filter results on properties or structure using SMARTS patterns or fragments drawn with the molecular editor to visualize those which include or exclude the specified fragment | ✓ | |
| Enable or disable filters using a toggle button | ✓ | |
| Cluster results into separate chemotypes based on Murcko scaffolds | ✓ | |
| Cluster results using skeletons or substitution patterns | ✓ | |
| View results and associated data in a tiled layout to see multiple structures at a glance | ✓ | |
| Multi-parameter scoring | | |
| Define a scoring profile that combines bioisosterism and physico-chemical properties | ✓ | |
| View the physical properties of result molecules in an intuitive radial plot | ✓ | |
| Assess overall multi-parameter molecule profile using radial plots and colors | ✓ | |
| Summarize property profile into a single radial plot score | ✓ | |
| Perform Multi-Parameter Scoring by filtering and ranking molecules according to radial plot score | ✓ | |
| Ensure that every new idea meets corporate or project guidelines for standard physical properties (e.g. logP, TPSA, MW etc.) | ✓ | |
| Ensure that conformations for new ideas are realistic by monitoring the torsion frequency in the CSD | ✓ | |
| Mark specific results as favorites for further investigation | ✓ | |
| Tag specific results with a custom label for further investigation | ✓ | |
| Assess chemical feasibility of new ideas by monitoring the attachment point atom type | ✓ | ✓ |
| Import or export custom radial plot properties | ✓ | |
| Database management |
| Create custom databases by fragmenting your corporate database | ✓ | ✓ |
| Control the size and flexibility of fragments that are stored in the database | ✓ | ✓ |
| Convert your available reagents into databases to search today using easily understood yet comprehensive rules | ✓ | ✓ |
| Create your own rules for conversion of reagents into fragment databases to be searched | ✓ | ✓ |
| View which databases need updating before you start a search | ✓ | |
| Filter by name to easily locate the databases you want to search or update | ✓ | |
| Update all or select the desired Spark databases in one go | ✓ | ✓ |
| Workflow integrations |
| Import your Spark project direclty into Flare to help you prioritize, via a wide portfolio of ideas and methods, the best molecules to make | ✓ | |
| Import ligands from a csv (structures read in from a SMILES strings) | ✓ | |
| Access the RDKit cheminformatics toolkit | | ✓ |
| Deploy in a standard workflow in KNIME | | ✓ |
| Export results as csv for use in Excel, Spotfire etc. (structures are exported as SMILES strings) | ✓ | |
| Export MEP surfaces as the CCP4, Cube, Insight and MOE file formats | ✓ | |
| Start a Blaze™ virtual screening experiment on millions of compounds from the GUI | ✓ | |
| Browse and retrieve Blaze search results directly, visualizing enrichment plot and statistics for each Blaze refinement level | ✓ | ✓ |
| Create and automate workflows using the Python® API | ✓ | ✓ |
| Upgrade Flare with Python modules for graphing, statistics, Jupyter® Notebook | ✓ | ✓ |
| Expand the functionality of the Flare GUI using Python extensions | ✓ | ✓ |
| Export Spark search calculations from the GUI and run them with pyFlare | ✓ | |
| Automate and distribute Spark calculations using pyFlare and Cresset released Python scripts and snippets | | Add-on |
