FEP+

High-performance free energy calculations for drug discovery

Life Science: FEP+

Discover better quality molecules, faster with FEP+

FEP+ is Schrödinger’s proprietary, physics-based free energy perturbation technology for computationally predicting protein-ligand binding at an accuracy matching experimental methods, across broad chemical space.

Explore vast chemical space and reduce costs

Leverage FEP+ as an accurate in silico binding affinity assay to drive rapid virtual design cycles and focus experimental efforts on only the highest quality ideas

Improve molecular profiles, efficiently

Optimize multiple properties simultaneously, including potency, selectivity, and solubility, to improve the profile and developability of small and large molecules

Pursue novel chemistry with confidence

Synthesize novel and challenging chemistry with a high degree of confidence through prospective application of FEP+

Continuously pushing the state of the art in free energy methods

Gold standard accuracy

Predictive accuracy approaching experiment (1 kcal/mol) as demonstrated in large-scale validation studies across diverse ligands and protein classes

Proven impact in drug discovery

Widely adopted by leading pharma and biotech companies, with several drug candidates in the clinic driven by FEP+

Highly versatile

Supports the broadest range of applications and perturbation types common in drug discovery scenarios and consistently expanded through active R&D

Apply FEP+ to diverse applications across the drug discovery process

Structure Prediction & Target Enablement

Structure Prediction & Target Enablement

  • Check greenValidate protein models without experimental structures or from low resolution structures using IFD-MD with FEP+
  • Check greenStructurally enable off-targets and design out common ADMET liabilities
Hit Discovery

Hit Discovery

  • Check greenRescore hits from virtual screens to prioritize synthesis lists and improve using absolute binding FEP+

  • Check greenLeverage available chemical matter to efficiently discover novel cores via core hopping 

  • Check greenPerform large-scale in silico fragment screens using absolute binding FEP+ and solubility FEP+
Hit-to-Lead & Lead Optimization

Hit-to-Lead & Lead Optimization

  • Check greenRapidly optimize on-target potency by leveraging FEP+ as an in silico binding affinity assay

  • Check greenOptimize selectivity to known off-targets and across large gene families

  • Check greenMaintain on-target potency and selectivity while optimizing ADMET properties
In Silico Protein Engineering

In Silico Protein Engineering

  • Check greenRefine antibody candidate selection with accuracy that reproduces experimentally determined relative free energies
  • Check greenPredict binding affinity, selectivity, and thermostability of peptides
  • Check greenEngineer enzymes for substrate selectivity and specificity

Accelerate FEP+ calculations across large compound libraries with Active Learning

Leverage a well-validated, automated workflow which trains a machine learning model on project-specific FEP+ data to allow processing of up to millions of compounds with highly accurate FEP+ calculations efficiently.

Technology in action

With FEP+, “The Experiment is the Limit.” Blog Life Science
With FEP+, “The Experiment is the Limit.”

High-performance free energy calculations for drug discovery

Tackling Drug Solubility: AbbVie and Schrödinger Collaborate to Advance Accurate Prediction Methods (FEP) Blog Life Science
Can AlphaFold Models be Used for Structure-Based Drug Design? A Perspective Two Years In Blog Life Science
Featured CourseFree energy calculations for drug design with FEP+

Learn how to apply FEP+ to your project with our online certification course

Level-up your FEP+ skills and enroll in our online molecular modeling course, Free Energy Calculations for Drug Design with FEP+.

View Course

Case Studies

Discover how Schrödinger’s technology is being used to solve real-world research challenges.

Hit to development candidate in 10 months: Rapid discovery of a novel, potent MALT1 inhibitor

Digital chemistry platform provides scale and accuracy to drive high precision molecular design

Morphic Therapeutic leverages digital chemistry strategy to design a novel small molecule inhibitor of α4β7 integrin

Collaborative enterprise platform and physics-based digital assays empower a team of experts to tackle a challenging target

Accelerating DMTA cycles with fast, push-button free energy calculations available to whole project teams

Single-edge FEP+ integrated in LiveDesign

Official NVIDIA Partner

Schrödinger has a strategic partnership with NVIDIA to optimize our computational drug discovery platform for NVIDIA GPU technology.

Documentation & Tutorials

Get answers to common questions and learn best practices for using Schrödinger’s software.

Life Science Documentation

Learning Path: Virtual Screening

A structured overview of how to construct a virtual screening pipeline.

Life Science Tutorial

Protein pKa Prediction with Constant pH Molecular Dynamics

Determine pKa values and protonation states for protein residues.

Life Science Tutorial

Introduction to Protein Thermostability Prediction using Protein FEP+

Increase protein thermostability by filling a buried cavity through mutation with protein FEP+.

Life Science Tutorial

Ligand Binding Pose Prediction for FEP+ using Core-Constrained Docking

Generate starting poses for FEP simulations for a series of BACE1 inhibitors using core constrained docking.

Life Science Tutorial

Identifying impactful mutations using FEP+ residue scanning

Perform an FEP+ residue scan for identifying the impact of mutations on the stability and affinity of a protein-protein system.

Life Science Tutorial

FEP Solubility

Perform a Free Energy of Perturbation (FEP) Solubility simulation on ibuprofen.

Materials Science Tutorial

FEP Solubility

Perform a Free Energy of Perturbation (FEP) Solubility simulation on ibuprofen.

Life Science Tutorial

BACE1 Inhibitor Design Using Free Energy Perturbation

Prepare, run, and analyze a free energy perturbation (FEP) simulation for a series of BACE1 inhibitors using FEP+.

Life Science Tutorial

Obtaining Protein Free Energy Perturbation Thermostability Predictions for Single Point Mutations

Prepare, run and analyze a protein FEP simulation to obtain thermostability predictions for single point mutations in the T4 Lysozyme

Materials Science Documentation

Materials Science Panel Explorer

Quickly learn which Schrödinger tools are the best fit for your research.

Related Products

Learn more about the related computational technologies available to progress your research projects.

Active Learning Applications

Accelerate discovery with machine learning

De Novo Design Workflow

Fully-integrated, cloud-based design system for ultra-large scale chemical space exploration and refinement

OPLS4 & OPLS5 Force Field

A modern, comprehensive force field for accurate molecular simulations

IFD-MD

Accurate ligand binding mode prediction for novel chemical matter, for on-targets and off-targets

Maestro

Complete modeling environment for your molecular discovery

LiveDesign

Your complete digital molecular design lab

Publications

Browse the list of peer-reviewed publications using Schrödinger technology in related application areas.

Life Science Publication

Enabling in-silico Hit Discovery Workflows Targeting RNA with Small Molecules

Life Science Publication

Active Learning FEP: Impact on Performance of AL Protocol and Chemical Diversity

Life Science Publication

Exploiting solvent exposed salt-bridge interactions for the discovery of potent inhibitors of SOS1 using free-energy perturbation simulations

Life Science Publication

Predicting Resistance to Small Molecule Kinase Inhibitors

Life Science Publication

Accurate physics-based prediction of binding affinities of RNA- and DNA-targeting ligands

Life Science Publication

Structure-based discovery and development of highly potent dihydroorotate dehydrogenase inhibitors for malaria chemoprevention

Life Science Publication

Leveraging the thermodynamics of protein conformations in drug discovery

Life Science Publication

In silico enabled discovery of KAI-11101, a preclinical DLK inhibitor for the treatment of neurodegenerative disease and neuronal injury

Life Science Publication

Discovery of a novel mutant-selective epidermal growth factor receptor inhibitor using an in silico enabled drug discovery platform

Life Science Publication

The Discovery of MORF-627, a Highly Selective Conformationally-Biased Zwitterionic Integrin αvβ6 Inhibitor for Fibrosis

Training & Resources

Online certification courses

Level up your skill set with hands-on, online molecular modeling courses. These self-paced courses cover a range of scientific topics and include access to Schrödinger software and support.

Tutorials

Learn how to deploy the technology and best practices of Schrödinger software for your project success. Find training resources, tutorials, quick start guides, videos, and more.