FEP+ for Biologics
High-performance free energy calculations for biologics discovery
Engineer better proteins, faster with FEP+
FEP+ is Schrödinger’s proprietary, physics-based free energy perturbation technology. Use FEP+ in your biologics discovery projects to computationally predict protein mutation effects at an accuracy matching experimental methods to within ~1 kcal/mol.
Reduce time-to-results from months to weeks by discarding irrelevant mutations early, as well as quickly generating new ideas and follow-up designs
Lower protein optimization costs compared to traditional directed evolution wet lab protocols by running fewer cycles and assaying fewer variants
Identify better quality candidates through simultaneous optimization of multiple parameters to facilitate more rapid testing and triaging of ideas
Key application areas
Affinity engineering
Enhance or decrease binding affinity of a protein to its target
Selectivity engineering
Tune preferential binding of a protein to one target over another
Cross-reactivity engineering
Extending breadth of binding across multiple targets
pH-dependent binding
Engineer pH-dependent association or dissociation between two proteins
Stability engineering
Enhance physical stability of a protein-based biologic
Developability assessment
Optimize properties like solubility, chemical stability, and physical stability
Benefit from Schrödinger’s proven protein engineering technologies
Protein FEP+
Accurately quantify the effects of mutations on protein stability and protein-protein binding affinities during the optimization of antibodies, antigens, peptides, enzymes, and other biologic products.
FEP+ Residue Scan
Rapidly model single mutations on multiple sites simultaneously to achieve consistent and reliable prediction of mutational effects and dramatically improve the efficiency of FEP+ calculations.
Schrödinger’s customizable protein engineering workflow
Our workflow leverages FEP+ Residue Scan and Protein FEP+ technologies to enable precise and efficient exploration of protein mutations to simultaneously optimize stability, binding affinity, specificity, pH-dependent binding, and cross-reactivity.
FEP+ Residue Scan offers 7X improvements in accuracy over MM/GBSA and up to 20X speedup over Protein FEP+
Correlation plots between MM/GBSA, FEP+ Residue Scan and Protein FEP+ calculations (y-axis), and relative experimental affinity measurements (x-axis), shown in kcal/mol. All calculations performed on the same system, mutations to and from proline currently excluded from FEP+ Residue Scan results. Pearson correlation coefficient (R2) shown at top left of each plot.
Broad application across protein-based therapeutics discovery
Access refined workflows across multiple biological modalities
Publications
Robust prediction of relative binding energies for protein-protein complex mutations using free energy perturbation calculations.
Sampson, et al. J Mol Biol. 2024, 436, 16.
Accurate prediction of protein thermodynamic stability changes upon residue mutation using free energy perturbation.
Scarabelli G, et al. J Mol Biol. 2022, 434, 2.
Potency- and selectivity-enhancing mutations of conotoxins for nicotinic acetylcholine receptors can be predicted using accurate free-energy calculations
Katz D, et al. Mar. Drugs 2021, 19(7), 367.
Target-template relationships in protein structure prediction and their effect on the accuracy of thermostability calculations
Lihan M, et al. Prot Sci. 2023, 32, 2, e4557.
Basic residues at position 11 of α-Conotoxin LvIA influence subtype selectivity between α3β2 and α3β4 nicotinic receptors via an electrostatic mechanism.
Haufe Y, et al. ACS Chem Neurosci. 2023, 14, 24, 4311–4322.
What is free energy perturbation (FEP)?
If you’re new to using FEP+, get a refresher on the fundamental concepts of relative binding free energy perturbation (FEP) calculations.
Documentation & Tutorials
Get answers to common questions and learn best practices for using Schrödinger’s software.
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