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 Webinar

Schrödinger デジタル創薬セミナー: Impacting drug discovery programs with large-scale de novo design

高品質な化学物質の創製をより包括的かつ効果的に可能にする技術の開発は、薬物探索の長年の目標でした。

Life Science Webinar

Impacting Drug Discovery Programs with Large-Scale De Novo Design

Developing technologies to more comprehensively and effectively enable de novo design of high-quality chemical matter has been a long-standing goal of drug discovery.

Life Science Webinar

Chinese Webinar: 薛定谔中文讲座:DLK在计算机辅助药物设计中的案例研究 ,网络讲座录制 计算机驱动用于治疗神经退行性疾病的高效、高选择性和穿透脑血屏障的DLK抑制剂的发现

双亮氨酸拉链激酶(DLK)(又名MAP3K12)是混合系谱激酶(MLK)家族的成员,它包含一个N-末端激酶结构域,后面跟着两个亮氨酸拉链结构域以及一个富含甘氨酸/丝氨酸/脯氨酸的C-末端结构域。它主要在神经元细胞中表达,特别是在神经元的突触末端和轴突中

Life Science Webinar

In silico enabled discovery of KAI-11101, a potent, selective, and brain-penetrant DLK inhibitor for the treatment of neurodegenerative diseases

In this webinar, we detail the program led by Schrödinger Therapeutics Group to discover a novel, potent, selective, and brain-penetrant DLK inhibitor (KAI-11101).

Life Science Webinar

In Silico Driven Drug Discovery of a Zwitterionic Integrin αvβ6 Development Candidate for Fibrosis

In this webinar, discover how in silico techniques combined with traditional medicinal chemistry approaches are applied in a structure-based drug discovery program.

Life Science Webinar

Structure-Based Drug Discovery Without a Structure: Enabling Accurate FEP+ Predictions for Challenging Targets and ADMET Anti-Targets

In this webinar, we showcase the successful utilization of unique technologies and dedicated workflows to enable accurate FEP+ predictions.

Life Science Webinar

Japanese: Schrödinger デジタル創薬セミナー Structure Based Drug Discovery without a Structure -Enabling Accurate FEP+ Predictions for Challenging Targets and ADMET Anti Targets

During this webinar, we will showcase the successful utilization of unique technologies and dedicated workflows to enable accurate FEP+ predictions.

Life Science Webinar

Beyond the Lab: Unleashing the Potential of In Silico Modeling in Drug Product Formulation

In this webinar, we explore Schrödinger’s leading molecular modeling and machine learning platform.

Life Science Webinar

Design of a Highly Selective, Allosteric, Picomolar TYK2 Inhibitor in Clinical Development

In this webinar, we highlight key moments from the discovery of this potentially best-in-class selective, allosteric, picomolar inhibitor of TYK2.

Life Science Webinar

Chinese: Physics-based Design of Bifunctional Degraders, Virtual 基于物理理论设计的双功能降解剂,网络讲座录制

具有两个配体和一个 Linker 的双功能 分子能够结合E3连接酶与靶蛋白,从而促使靶蛋白降解。

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.