ArticleJournal of computer-aided molecular design2014
Virtual screening of integrase inhibitors by large scale binding free energy calculations: the SAMPL4 challenge.
Article in Journal of computer-aided molecular design, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed.
- Toward Reconciling the Standard Binding Free Energy of Lenacapavir to HIV-1 Capsid with Experiment: Thermodynamic Effects of Solvent Buffer and Ligand Reorganization.The journal of physical chemistry. B · 2026Article
- Relative Binding Free Energy Estimation of Congeneric Ligands and Macromolecular Mutants with the Alchemical Transfer Method with Coordinate Swapping.Journal of chemical information and modeling · 2025Article
- Binding Selectivity Analysis from Alchemical Receptor Hopping and Swapping Free Energy Calculations.The journal of physical chemistry. B · 2024Article
- What to Make of Zero: Resolving the Statistical Noise from Conformational Reorganization in Alchemical Binding Free Energy Estimates with Metadynamics Sampling.Journal of chemical theory and computation · 2024Article
- Structure-based virtual screening workflow to identify antivirals targeting HIV-1 capsid.Journal of computer-aided molecular design · 2022Article
- Application of the alchemical transfer and potential of mean force methods to the SAMPL8 host-guest blinded challenge.Journal of computer-aided molecular design · 2022Article
- Domino C-C/C-O bond formation: palladium-catalyzed regioselective synthesis of 7-iodobenzo[RSC advances · 2021Article
- Evaluation of log P, pKJournal of computer-aided molecular design · 2021Article
- Protein storytelling through physics.Science (New York, N.Y.) · 2020Review
- Best Practices for Alchemical Free Energy Calculations [Article v1.0].Living journal of computational molecular science · 2020Article
- De Novo Prediction of Binders and Nonbinders for T4 Lysozyme by gREST Simulations.Journal of chemical information and modeling · 2019Article
- Massive-Scale Binding Free Energy Simulations of HIV Integrase Complexes Using Asynchronous Replica Exchange Framework Implemented on the IBM WCG Distributed Network.Journal of chemical information and modeling · 2019Article
- Inclusion of enclosed hydration effects in the binding free energy estimation of dopamine D3 receptor complexes.PloS one · 2019Article
- Improving Prediction Accuracy of Binding Free Energies and Poses of HIV Integrase Complexes Using the Binding Energy Distribution Analysis Method with Flattening Potentials.Journal of chemical information and modeling · 2018Article
- Comparing alchemical and physical pathway methods for computing the absolute binding free energy of charged ligands.Physical chemistry chemical physics : PCCP · 2018Article
- Binding Modes of Ligands Using Enhanced Sampling (BLUES): Rapid Decorrelation of Ligand Binding Modes via Nonequilibrium Candidate Monte Carlo.The journal of physical chemistry. B · 2018Article
- Assessment of a Single Decoupling Alchemical Approach for the Calculation of the Absolute Binding Free Energies of Protein-Peptide Complexes.Frontiers in molecular biosciences · 2018Article
- Approaches for calculating solvation free energies and enthalpies demonstrated with an update of the FreeSolv database.Journal of chemical and engineering data · 2017Article
- Absolute binding free energy calculations of CBClip host-guest systems in the SAMPL5 blind challenge.Journal of computer-aided molecular design · 2017Article
- A combined treatment of hydration and dynamical effects for the modeling of host-guest binding thermodynamics: the SAMPL5 blinded challenge.Journal of computer-aided molecular design · 2017Article
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Authors and funding
9 authors.
Funding
Abstract
As part of the SAMPL4 blind challenge, filtered AutoDock Vina ligand docking predictions and large scale binding energy distribution analysis method binding free energy calculations have been applied to the virtual screening of a focused library of candidate binders to the LEDGF site of the HIV integrase protein. The computational protocol leveraged docking and high level atomistic models to improve enrichment. The enrichment factor of our blind predictions ranked best among all of the computational submissions, and second best overall. This work represents to our knowledge the first example of the application of an all-atom physics-based binding free energy model to large scale virtual screening. A total of 285 parallel Hamiltonian replica exchange molecular dynamics absolute protein-ligand binding free energy simulations were conducted starting from docked poses. The setup of the simulations was fully automated, calculations were distributed on multiple computing resources and were completed in a 6-weeks period. The accuracy of the docked poses and the inclusion of intramolecular strain and entropic losses in the binding free energy estimates were the major factors behind the success of the method. Lack of sufficient time and computing resources to investigate additional protonation states of the ligands was a major cause of mispredictions. The experiment demonstrated the applicability of binding free energy modeling to improve hit rates in challenging virtual screening of focused ligand libraries during lead optimization.
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