Software

Cresset Pipeline Pilot integration

Introduction

Cresset’s unique solutions are available through easy to use graphical user interfaces, command lines and through workflow solutions such as Pipeline Pilot™ and KNIME™. Using the Pipeline Pilot interface enables integration of our approach into standard workflows and with other applications. We provide access to all our applications through Pipeline Pilot components that call the corresponding command line application behind the scenes.

Blaze™ components

Blaze is Cresset’s virtual screening platform that is optimized to find novel, diverse hits for your project. Blaze uses Cresset’s unique field technology to generate hits that are similar in electrostatics and shape space to the query molecule, but with diverse 2D structures. It runs on a Linux or GPU cluster and is designed to manage compounds, collections, conformations, job distribution and searches.

The Blaze components are:

  • New Blaze Search: Start a Blaze search
  • Blaze Searches Viewer: Report the list and status of all Blaze searches
  • Detailed Blaze Search Viewer: Report detailed information on a specific Blaze search
  • Download Blaze Search Results: Retrieves the results from a Blaze search
  • Upload Molecules to Blaze Collection: Update collections in Blaze
  • Blaze Status Viewer: Report the status of the Blaze server and any running jobs

Forge™ components

Forge is a powerful ligand-focused workbench for understanding SAR and design. In Pipeline Pilot the Forge components enable ligand comparisons and investigation, building of qualitative and quantitative 3D models of activity, scoring of new molecule designs, creation of molecular similarity and disparity matrices and building of detailed pharmacophores.

Machine Learning example protocolThe Forge components are:

  • Forge Align: Align and score molecules to a 3D reference molecule using electrostatics and shape or common substructure; molecules are conformationally hunted if necessary
  • FieldTemplater™: Compare molecules using their electrostatics, shape and hydrophobic fields in order to find common pharmacophores
  • Activity Miner™: Generate similarity, distance or disparity matrix from a set of aligned molecules using 2D and 3D measures of similarity
  • Forge Build: Generate regression and classification models for activity using Forge 3D-QSAR or Machine Learning methods (k-Nearest Neighbor, Random Forest, Relevance Vector Machines and Support Vector Machines)
  • Forge Score: Predict activities for molecules using a regression or classification model generated with Forge Build
  • Forge Model Viewer (on Client): Launch Forge to view Forge models generated with Forge Build
  • Forge Surface Writer: Generate the electrostatic, shape and hydrophobic field surfaces for the input molecules

Spark™ components

Spark enables you to move to new series and non-obvious IP by swapping scaffolds and exploring accessible R-groups. Given a ‘starter molecule’, you can select a section to replace and Spark will suggest a list of new molecules containing replacement moieties with similar electrostatic and steric properties. Spark comes with several databases of moieties generated from fragmentation of commercially-available compounds, active molecules reported in the literature and available reagents. In addition you are able to generate your own databases of replacement moieties using the database generator functionality.

In Pipeline Pilot the Spark components provide access to the scaffold hopping and R-group exploring capabilities with a specialized component to enable graphical specification of the portion of the starter molecule to be replaced. Lastly a database creation component is included.

The Spark components are:

  • Spark Database Search: Search databases for novel scaffolds or R-groups for a specified molecule
  • Spark Database Search (on Client): As above except it enables the graphical selection of the region to be replaced by
  • Spark in a database search experiment. This component calls a locally installed copy of Spark
  • Generate Spark Database: Generate or update Spark databases of fragments or reagents
  • Spark Database List Viewer: List all available databases for Spark

Flare™ components

Flare is a structure-based design tool for the visualization and analysis of protein-ligand complexes. With Flare, you can gain vital knowledge of protein and ligand electrostatics to perfect new molecule design, predict activity for new molecule designs using Electrostatic Complementarity™ scoring, design new molecules and dock them to your protein target, minimize your protein-ligand complex to achieve the optimal interaction for each compound, calculate the location and stability of water molecules in your protein, use the energetics of ligand binding to guide lead optimization.

In Pipeline Pilot the Flare components enable full access to the Flare functionality through the Flare Python API.

The Flare components are:

  • pyflare: Runs a Python script which has access the Flare Python API

XedTools™ components

The XedTools components give access to core technologies such as ligand minimization and conformation generation. They are:

  • XedMin™: Ligand minimizer (using Cresset’s proprietary XED force field) to optimize ligands in isolation or in a specified context such as the protein active site
  • XedeX™: Create low energy, diverse conformation populations for a ligand

Viewers components

Cresset supplies two generic viewer components which call the main graphical user interfaces on the client machine. They are:

  • Forge Molecule Viewer (on Client): Useful for visualizing the electrostatic fields around the input molecule or for viewing the results of other Cresset components
  • Flare Ligand and Protein Viewer (on Client): Launches Flare to view ligand and protein structures

Installation

The Cresset Pipeline Pilot components wrap functionality of key binaries and hence both the application binaries and the Cresset Pipeline Pilot Package must be installed. Read the installation instructions for the Cresset Pipeline Pilot Package.

Licensing

The software used by the Cresset Pipeline Pilot components requires a valid license file. Contact us for more information.

Examples

Cresset provides example workflows that encompass each of the Cresset Pipeline Pilot components. The examples are included in the installation package and can be found under Protocols > Examples > Chemistry > Cresset. Additional examples for Blaze that require configuration before they will execute (which prevents inclusion in the installation package) are available for download here.

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