flare
Free Energy Perturbation (FEP)
Smarter and faster FEP calculations
Developed in collaboration with Prof. Julien Michel at the University of Edinburgh, FEP in Flare™ combines open-source tools such as AMBER tools, OpenMM, LOMAP, Sire and BioSimSpace with Cresset expertise in developing intuitive software to deliver an accessible and user friendly interface to a fully automated FEP workflow
Read the full Flare V4 release announcement
Assessment of Binding Affinity via Alchemical Free Energy Calculations J. Chem. Inf. Model. 2020
- Fully connected, two-ways networks, enable more accurate error estimation for each link and thorough analysis of cycle errors
- 'Production' mode experimental affinity values optimize the network by ensuring each new ligand to predict is never too far away (in terms of number of FEP transformations) from a ligand with known activity
- Given a parent ligand and protein, get accurate values for relative binding affinity within a related set of ligands
- Generate your ligand starting poses by aligning them to the parent ligand using Flare’s alignment feature, or dock them into the protein associated with your FEP project
- Automatically generate the perturbation network with options to refine the map to ensure it is exactly as you want
- Configure calculations to enhance results (simulation time and number of λ windows)
- Optimize calculation time by using the Cresset Engine Broker to connect to a local cluster or cloud computing facilities
- View all aspects of your FEP calculation results in a dedicated window and identify problematic transformations
- Fully validated against literature benchmarks
- Seamless protein and ligand setup in GUI
FEP calculations in Flare
FEP calculations in Flare
FEP calculations in Flare
FEP calculations in Flare
Fully connected networks introduce some redundancy to the network, enabling more precise calculations. In production mode, the blue links connect ligands with known experimental affinity, and will not be calculated
‘Star graph’ networks are ideal for the optimization of a single lead compound, shown in the centre of the network
Development of custom AMBER/GAFF2 and AMBER/GAFF parameters is made simple by the Custom Force Field wizard
Custom Force Field Parameter explorer
New visual tools for the analysis of Dynamics simulations in Flare V4
Watch Mark Mackey, Cresset CSO, presentation on 'Automated Assessment of Binding Affinity via Alchemical Free Energy Calculations' at 2020 Workshop Free Energy Methods in Drug Design, organized by the Chodera Lab.
FEP calculations in Flare
FEP calculations in Flare
FEP calculations in Flare
FEP calculations in Flare
Fully connected networks introduce some redundancy to the network, enabling more precise calculations. In production mode, the blue links connect ligands with known experimental affinity, and will not be calculated
‘Star graph’ networks are ideal for the optimization of a single lead compound, shown in the centre of the network
Development of custom AMBER/GAFF2 and AMBER/GAFF parameters is made simple by the Custom Force Field wizard
Custom Force Field Parameter explorer
New visual tools for the analysis of Dynamics simulations in Flare V4
FEP
Working with Dr Julien Michel at the University of Edinburgh UK, an expert in free energy methods, we combined and enhanced open-source tools to generate a robust, user-friendly, fully validated and accessible implementation of FEP. This enables computational chemists to predict the activities of new molecules during drug discovery, significantly reducing synthetic chemistry costs and improving the time to clinical candidate.
Mark Mackey, CSO, Cresset
I am delighted that the results from the Knowledge Transfer Partnership (KTP) / Innovate UK collaboration between my group and Cresset has been released within Flare V3. The interface designed by Cresset significantly streamlines and improves the workflow for using FEP based on open source tools developed by academic groups. This will accelerate the use of these exciting new techniques in commercial and academic laboratories worldwide.
Julien Michel, University of Edinburgh, UK
Flare
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