Estimation of relative free energies of binding using pre‐computed ensembles based on the single‐step free energy perturbation and the site‐identification by Ligand competitive saturation approaches
Sign Up to like & getrecommendations! Published in 2017 at "Journal of Computational Chemistry"
DOI: 10.1002/jcc.24522
Abstract: Accurate and rapid estimation of relative binding affinities of ligand‐protein complexes is a requirement of computational methods for their effective use in rational ligand design. Of the approaches commonly used, free energy perturbation (FEP) methods… read more here.
Keywords: energy; estimation relative; energy perturbation; relative free ... See more keywords
Free energy perturbation (FEP)-guided scaffold hopping
Sign Up to like & getrecommendations! Published in 2021 at "Acta Pharmaceutica Sinica B"
DOI: 10.1016/j.apsb.2021.09.027
Abstract: Abstract Scaffold hopping refers to computer-aided screening for active compounds with different structures against the same receptor to enrich privileged scaffolds, which is a topic of high interest in organic and medicinal chemistry. However, most… read more here.
Keywords: fep; perturbation fep; scaffold hopping; fep guided ... See more keywords
Integrating Machine Learning into Free Energy Perturbation Workflows
Sign Up to like & getrecommendations! Published in 2025 at "Journal of Chemical Information and Modeling"
DOI: 10.1021/acs.jcim.5c01449
Abstract: Free energy perturbation (FEP) methods are among the most accurate tools in structure-based drug design for predicting protein–ligand binding affinities. However, their adoption remains limited due to high computational demands and complex setup procedures. This… read more here.
Keywords: integrating machine; machine learning; free energy; energy perturbation ... See more keywords
Free Energy Perturbation Simulations Measure the Change in Binding Affinity of the Aβ25–35 Peptide to the Zwitterionic Bilayer Caused by Oxidation
Sign Up to like & getrecommendations! Published in 2025 at "Journal of Chemical Information and Modeling"
DOI: 10.1021/acs.jcim.5c02148
Abstract: We designed and employed a relative free energy perturbation (FEP) combined with replica exchange with solute tempering (REST) all-atom molecular dynamics to investigate how Met35 oxidation affects the free energy of binding of the Aβ25–35… read more here.
Keywords: met35 oxidation; free energy; energy perturbation; oxidation ... See more keywords
Application of Free Energy Perturbation (FEP+) to Understanding Ligand Selectivity: A Case Study to Assess Selectivity Between Pairs of Phosphodiesterases (PDE's)
Sign Up to like & getrecommendations! Published in 2019 at "Journal of chemical information and modeling"
DOI: 10.1021/acs.jcim.9b00106
Abstract: Cyclic nucleotide phosphodiesterases (PDE's) are metalloenzymes that play a key role in regulating the levels of the ubiquitous second messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). In humans, 11 PDE protein families… read more here.
Keywords: phosphodiesterases pde; perturbation fep; study; energy perturbation ... See more keywords
Induced-Fit Docking Enables Accurate Free Energy Perturbation Calculations in Homology Models.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of chemical theory and computation"
DOI: 10.1021/acs.jctc.2c00371
Abstract: Homology models have been used for virtual screening and to understand the binding mode of a known active compound; however, rarely have the models been shown to be of sufficient accuracy, comparable to crystal structures,… read more here.
Keywords: energy perturbation; induced fit; homology models; free energy ... See more keywords
Reliable and Accurate Prediction of Single-Residue pKa Values through Free Energy Perturbation Calculations.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of chemical theory and computation"
DOI: 10.1021/acs.jctc.2c00954
Abstract: Accurate prediction of the pKa's of protein residues is crucial to many applications in biological simulation and drug discovery. Here, we present the use of free energy perturbation (FEP) calculations for the prediction of single-protein… read more here.
Keywords: energy perturbation; accurate prediction; free energy; pka values ... See more keywords
Machine Learning Guided AQFEP: A Fast and Efficient Absolute Free Energy Perturbation Solution for Virtual Screening
Sign Up to like & getrecommendations! Published in 2024 at "Journal of Chemical Theory and Computation"
DOI: 10.1021/acs.jctc.4c00399
Abstract: Structure-based methods in drug discovery have become an integral part of the modern drug discovery process. The power of virtual screening lies in its ability to rapidly and cost-effectively explore enormous chemical spaces to select… read more here.
Keywords: virtual screening; energy; absolute free; free energy ... See more keywords
Exploring the Activity Profile of TbrPDEB1 and hPDE4 Inhibitors Using Free Energy Perturbation
Sign Up to like & getrecommendations! Published in 2022 at "ACS Medicinal Chemistry Letters"
DOI: 10.1021/acsmedchemlett.1c00690
Abstract: Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the parasite Trypanosoma brucei (T.b.). A validated target for the treatment of HAT is the parasitic T.b. cyclic nucleotide phosphodiesterase B1 (TbrPDEB1). Although nanomolar… read more here.
Keywords: energy perturbation; tbrpdeb1 inhibitors; free energy; tbrpdeb1 ... See more keywords
Benchmarking HelixFold3-Predicted Holo Structures for Relative Free Energy Perturbation Calculations
Sign Up to like & getrecommendations! Published in 2024 at "ACS Omega"
DOI: 10.1021/acsomega.4c11413
Abstract: AlphaFold2 demonstrated remarkable capabilities for protein structure prediction. However, it is limited to downstream tasks, such as ligand docking and free energy calculations, as it cannot predict holo structures with bound ligands. AlphaFold3, a state-of-the-art… read more here.
Keywords: energy; structure; free energy; energy perturbation ... See more keywords
Narrowing the gap between machine learning scoring functions and free energy perturbation using augmented data
Sign Up to like & getrecommendations! Published in 2025 at "Communications Chemistry"
DOI: 10.1038/s42004-025-01428-y
Abstract: Machine learning offers great promise for fast and accurate binding affinity predictions. However, current models lack robust evaluation and fail on tasks encountered in (hit-to-) lead optimisation, such as ranking the binding affinity of a… read more here.
Keywords: energy perturbation; free energy; machine; machine learning ... See more keywords