ArticleCommunications chemistry2023
The maximal and current accuracy of rigorous protein-ligand binding free energy calculations.
Article in Communications chemistry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
What it found
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Who cites it
99 citing papers in PubMed.
- A Functional Investigation of Antibody Fc-FcRn Variant Binding Guided by In Silico Free Energy Perturbation Methods.Journal of molecular biology · 2026Article
- Computational identification of potential inhibitors for chikungunya virus nsP2pro.Royal Society open science · 2026Article
- A critical appraisal of structure-based virtual screening, binding free energy methods, and AI-driven molecular design across the evolving computational landscape of drug discovery.Journal of computer-aided molecular design · 2026Review
- Training a force field for proteins and small molecules from scratch.Chemical science · 2026Article
- Evaluating molecular docking for binding affinity predictions: a systematic analysis of key parameters and the utility of AlphaFold2 structures for the Schrödinger dataset.Journal of computer-aided molecular design · 2026Article
- One Blob to Rule Them All: A Universal Dual-Topology Nonequilibrium Framework for Relative and Absolute Binding Free Energies via a Lennard-Jones Blob Reference.Journal of chemical theory and computation · 2026Article
- A systematic evaluation framework for universal antibody-antigen binding affinity prediction and candidate recommendation.iScience · 2026Article
- On the generalization and usability of cofolding models for GPCR drug discovery.npj drug discovery · 2026Article
- Molecular Dynamics and Free Energy Calculations Predict Binding Mode and Affinity Determinants of Specialized Pro-Resolving Mediators at GPR101.ACS omega · 2026Article
- Machine Learning for RNA-Targeting Drug Design.Journal of chemical information and modeling · 2026Review
- Benchmarking Docking Protocols on Predicting Alternative Binding Modes.Journal of chemical information and modeling · 2026Article
- Towards spatial lipid profiling by using mass spectrometry: analytical challenges and applications.Analytical and bioanalytical chemistry · 2026Review
- Enhancing Relative Binding Free Energy Calculation with Grand Canonical Monte Carlo, Water-swap Monte Carlo, Terminal-flip Monte Carlo and Replica Exchange Solute Tempering.Journal of chemical theory and computation · 2026Article
- An orally available PfPKG inhibitor blocks Plasmodium's infection of the liver.PLoS pathogens · 2026Article
- ModBindProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Discovery of 2H-Pyrrolo[3,4‑ACS medicinal chemistry letters · 2026Article
- Bioassay-Guided Phytochemical Investigation of VietnameseMolecules (Basel, Switzerland) · 2026Article
- Large-Scale Collaborative Assessment of Binding Free Energy Calculations for Drug Discovery Using OpenFE.Journal of chemical information and modeling · 2026Article
- Absolute Binding Free Energy Calculations between the SARS-CoV-2 Main Protease and 130 Drug Leads Using Implicit Ligand Theory.Journal of chemical information and modeling · 2026Article
- More protein-ligand data are needed for AlphaFold-like models to enable drug discovery.Current opinion in structural biology · 2026Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Computational techniques can speed up the identification of hits and accelerate the development of candidate molecules for drug discovery. Among techniques for predicting relative binding affinities, the most consistently accurate is free energy perturbation (FEP), a class of rigorous physics-based methods. However, uncertainty remains about how accurate FEP is and can ever be. Here, we present what we believe to be the largest publicly available dataset of proteins and congeneric series of small molecules, and assess the accuracy of the leading FEP workflow. To ascertain the limit of achievable accuracy, we also survey the reproducibility of experimental relative affinity measurements. We find a wide variability in experimental accuracy and a correspondence between binding and functional assays. When careful preparation of protein and ligand structures is undertaken, FEP can achieve accuracy comparable to experimental reproducibility. Throughout, we highlight reliable protocols that can help maximize the accuracy of FEP in prospective studies.
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.