ArticleJournal of chemical theory and computation2011
Improved Binding Free Energy Predictions from Single-Reference Thermodynamic Integration Augmented with Hamiltonian Replica Exchange.
Article in Journal of chemical theory and computation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Predicting absolute aqueous solubility by applying a machine learning model for an artificially liquid-state as proxy for the solid-state.Journal of computer-aided molecular design · 2023Article
- Accelerating Alchemical Free Energy Prediction Using a Multistate Method: Application to Multiple Kinases.Journal of chemical information and modeling · 2023Article
- Accelerated Enveloping Distribution Sampling (AEDS) Allows for Efficient Sampling of Orthogonal Degrees of Freedom.Journal of chemical information and modeling · 2023Article
- Dawn of a New Era for Membrane Protein Design.Biodesign research · 2022Review
- Coupling Coarse-Grained to Fine-Grained Models via Hamiltonian Replica Exchange.Journal of chemical theory and computation · 2020Article
- Exploring pH Dependent Host/Guest Binding Affinities.The journal of physical chemistry. B · 2020Article
- Predicting and Experimentally Validating Hot-Spot Residues at Protein-Protein Interfaces.ACS chemical biology · 2019Article
- Using AMBER18 for Relative Free Energy Calculations.Journal of chemical information and modeling · 2019Article
- Computation of protein-ligand binding free energies using quantum mechanical bespoke force fields.MedChemComm · 2019Article
- Potential Mean Force from Umbrella Sampling Simulations: What Can We Learn and What Is Missed?Journal of chemical theory and computation · 2019Article
- Rapid and accurate structure-based therapeutic peptide design using GPU accelerated thermodynamic integration.Proteins · 2019Article
- Predicting Binding Free Energies: Frontiers and Benchmarks.Annual review of biophysics · 2017Review
- A computational approach for designing D-proteins with non-canonical amino acid optimised binding affinity.PloS one · 2017Article
- Biomolecular Force Field Parameterization via Atoms-in-Molecule Electron Density Partitioning.Journal of chemical theory and computation · 2016Article
- Binding Energy Distribution Analysis Method: Hamiltonian Replica Exchange with Torsional Flattening for Binding Mode Prediction and Binding Free Energy Estimation.Journal of chemical theory and computation · 2016Article
- A Self-Adaptive Steered Molecular Dynamics Method Based on Minimization of Stretching Force Reveals the Binding Affinity of Protein-Ligand Complexes.Molecules (Basel, Switzerland) · 2015Article
- Accurate calculation of mutational effects on the thermodynamics of inhibitor binding to p38α MAP kinase: a combined computational and experimental study.Journal of chemical theory and computation · 2013Article
- Perspective: Alchemical free energy calculations for drug discovery.The Journal of chemical physics · 2012Article
- Fungal bis-Naphthopyrones as Inhibitors of Botulinum Neurotoxin Serotype A.ACS medicinal chemistry letters · 2012Article
- Conformational Transitions and Convergence of Absolute Binding Free Energy Calculations.Journal of chemical theory and computation · 2012Article
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Reliable predictions of relative binding free energies are essential in drug discovery, where chemists modify promising compounds with the aim of increasing binding affinity. Conventional Thermodynamic Integration (TI) approaches can estimate corresponding changes in binding free energies, but suffer from inadequate sampling due to ruggedness of the molecular energy surfaces. Here, we present an improved TI strategy for computing relative binding free energies of congeneric ligands. This strategy employs a specific, unphysical single-reference (SR) state and Hamiltonian replica exchange (HREX) to locally enhance sampling. We then apply this strategy to compute relative binding free energies of twelve ligands in the L99A mutant of T4 Lysozyme. Besides the ligands, our approach enhances hindered rotations of the important V111, as well as V87 and L118 sidechains. Concurrently, we devise practical strategies to monitor and improve HREX-SRTI efficiency. Overall, the HREX-SRTI results agree well (R(2) = 0.76, RMSE = 0.3 kcal/mol) with available experimental data. When optimized for efficiency, the HREX-SRTI precision matches that of experimental measurements.
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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.