ArticleCommunications chemistry2022
Evaluating the use of absolute binding free energy in the fragment optimisation process.
Article in Communications chemistry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed.
- Computational identification of potential inhibitors for chikungunya virus nsP2pro.Royal Society open science · 2026Article
- Fully Automatable Relative Binding Free Energy Calculations with Enhanced Sampling Using FAST/MBAR.Journal of chemical theory and computation · 2026Article
- Selection of Novel DNA Aptamers against HPV16 Biomarker, E6: AnACS omega · 2026Article
- FLOWR.ROOT - A flow matching-based foundation model for joint multi-purpose structure-aware 3D ligand generation and affinity prediction.Nature communications · 2026Article
- Molecular Dynamics Workflows to Compute Large-Scale Sets of Absolute Binding Free Energies Aiding Drug Candidate and Binding Pose Selection.Journal of chemical theory and computation · 2026Article
- An integrated experimental and computational pipeline for crystallographic fragment screening of membrane protein in the lipid cubic phase.Communications chemistry · 2026Article
- Dual-LAO for calculating fast and robust relative binding free energies of simple and complex transformations.Communications chemistry · 2026Article
- Efficient Binding Affinity Estimation for Fragment-Based Compounds Using a Separated Topologies Approach.Journal of chemical information and modeling · 2026Article
- Binding Free Energies without Alchemy.ArXiv · 2026Article
- A Computational Framework to Evaluate Interactions of BPA and Its Analogs with Human Liver X Receptor-Beta for Health Risk Assessment.Chemical research in toxicology · 2026Article
- A Relative Binding Free Energy Framework for Structurally Dissimilar Molecules.Journal of chemical information and modeling · 2026Article
- Developments and challenges in hit progression within fragment-based drug discovery.Nature communications · 2026Review
- BindFlow: A Free, User-Friendly Pipeline for Absolute Binding Free Energy Calculations Using Free Energy Perturbation or MM(PB/GB)SA.Journal of chemical theory and computation · 2026Article
- Molecular Mechanisms of Gain-of-Function Mutations in λ Cro Revealed by Molecular Dynamics Simulations.ACS physical chemistry Au · 2025Article
- Article
- Machine Learning-Enhanced Calculation of Quantum-Classical Binding Free Energies.Journal of chemical theory and computation · 2025Article
- Accelerating fragment-based drug discovery using grand canonical nonequilibrium candidate Monte Carlo.Nature communications · 2025Article
- Article
- Drugit: crowd-sourcing molecular design of non-peptidic VHL binders.Nature communications · 2025Article
- Assessment of the Topology and Oligomerisation States of Coiled Coils Using Metadynamics with Conformational Restraints.Journal of chemical theory and computation · 2025Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Key to the fragment optimisation process within drug design is the need to accurately capture the changes in affinity that are associated with a given set of chemical modifications. Due to the weakly binding nature of fragments, this has proven to be a challenging task, despite recent advancements in leveraging experimental and computational methods. In this work, we evaluate the use of Absolute Binding Free Energy (ABFE) calculations in guiding fragment optimisation decisions, retrospectively calculating binding free energies for 59 ligands across 4 fragment elaboration campaigns. We first demonstrate that ABFEs can be used to accurately rank fragment-sized binders with an overall Spearman's r of 0.89 and a Kendall τ of 0.67, although often deviating from experiment in absolute free energy values with an RMSE of 2.75 kcal/mol. We then also show that in several cases, retrospective fragment optimisation decisions can be supported by the ABFE calculations. Comparing against cheaper endpoint methods, namely N
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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.