ArticleJournal of computational chemistry2014
Net charge changes in the calculation of relative ligand-binding free energies via classical atomistic molecular dynamics simulation.
Article in Journal of computational chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 70 citations in OpenAlex.
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- Probing Limitations of Co-Alchemical Charge Changes in Free-Energy Calculations.Journal of chemical theory and computation · 2025Article
- Multistate Method to Efficiently Account for Tautomerism and Protonation in Alchemical Free-Energy Calculations.Journal of chemical theory and computation · 2024Article
- Guidelines for Free-Energy Calculations Involving Charge Changes.Journal of chemical theory and computation · 2024Article
- Designing of disruptor molecules to restrain the protein-protein interaction network of VANG1/SCRIB/NOS1AP using fragment-based drug discovery techniques.Molecular diversity · 2023Article
- Scaffold Hopping and Optimization of Small Molecule Soluble Adenyl Cyclase Inhibitors Led by Free Energy Perturbation.Journal of chemical information and modeling · 2023Article
- Non-Ewald methods for evaluating the electrostatic interactions of charge systems: similarity and difference.Biophysical reviews · 2022Review
- The Use of Molecular Dynamics Simulation Method to Quantitatively Evaluate the Affinity between HBV Antigen T Cell Epitope Peptides and HLA-A Molecules.International journal of molecular sciences · 2022Article
- Explicit solvation thermodynamics in ionic solution: extending grid inhomogeneous solvation theory to solvation free energy of salt-water mixtures.Journal of computer-aided molecular design · 2022Article
- Computational Tools for Accurate Binding Free-Energy Prediction.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Best practices for constructing, preparing, and evaluating protein-ligand binding affinity benchmarks [Article v0.1].Living journal of computational molecular science · 2022Article
- Generalizing the Discrete Gibbs Sampler-Based λ-Dynamics Approach for Multisite Sampling of Many Ligands.Journal of chemical theory and computation · 2021Article
- EfficientJournal of chemical information and modeling · 2021Article
- A Benchmark of Electrostatic Method Performance in Relative Binding Free Energy Calculations.Journal of chemical information and modeling · 2021Article
- The effect of different cutoff schemes in molecular simulations of proteins.Journal of computational chemistry · 2020Article
- Charge-Changing Perturbations and Path Sampling via Classical Molecular Dynamic Simulations of Simple Guest-Host Systems.Journal of chemical theory and computation · 2020Article
- Enhancing the promiscuity of a member of the Caspase protease family by rational design.Proteins · 2020Article
- Article
- DPP1 Inhibitors: Exploring the Role of Water in the S2 Pocket of DPP1 with Substituted Pyrrolidines.ACS medicinal chemistry letters · 2019Article
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2 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
The calculation of binding free energies of charged species to a target molecule is a frequently encountered problem in molecular dynamics studies of (bio-)chemical thermodynamics. Many important endogenous receptor-binding molecules, enzyme substrates, or drug molecules have a nonzero net charge. Absolute binding free energies, as well as binding free energies relative to another molecule with a different net charge will be affected by artifacts due to the used effective electrostatic interaction function and associated parameters (e.g., size of the computational box). In the present study, charging contributions to binding free energies of small oligoatomic ions to a series of model host cavities functionalized with different chemical groups are calculated with classical atomistic molecular dynamics simulation. Electrostatic interactions are treated using a lattice-summation scheme or a cutoff-truncation scheme with Barker-Watts reaction-field correction, and the simulations are conducted in boxes of different edge lengths. It is illustrated that the charging free energies of the guest molecules in water and in the host strongly depend on the applied methodology and that neglect of correction terms for the artifacts introduced by the finite size of the simulated system and the use of an effective electrostatic interaction function considerably impairs the thermodynamic interpretation of guest-host interactions. Application of correction terms for the various artifacts yields consistent results for the charging contribution to binding free energies and is thus a prerequisite for the valid interpretation or prediction of experimental data via molecular dynamics simulation. Analysis and correction of electrostatic artifacts according to the scheme proposed in the present study should therefore be considered an integral part of careful free-energy calculation studies if changes in the net charge are involved.
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