ArticleJournal of computer-aided molecular design2021
Enhancing water sampling of buried binding sites using nonequilibrium candidate Monte Carlo.
Article in Journal of computer-aided molecular design, 2021. 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.
- Fully Automatable Relative Binding Free Energy Calculations with Enhanced Sampling Using FAST/MBAR.Journal of chemical theory and computation · 2026Article
- 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
- Large-Scale Collaborative Assessment of Binding Free Energy Calculations for Drug Discovery Using OpenFE.Journal of chemical information and modeling · 2026Article
- A Quadrupolar Fullerene Model System for Benchmarking Enhanced Sampling of Trapped Waters in Free Energy Calculations.The journal of physical chemistry. B · 2026Article
- Solvation Free Energies of Drug-like Molecules via Fast Growth in an Explicit Solvent: Assessment of the AM1-BCC, RESP/HF/6-31G*, RESP-QM/MM, and ABCG2 Fixed-Charge Approaches.Journal of chemical theory and computation · 2025Article
- Current State of Open Source Force Fields in Protein-Ligand Binding Affinity Predictions.Journal of chemical information and modeling · 2024Article
- Efficient Sampling of Cavity Hydration in Proteins with Nonequilibrium Grand Canonical Monte Carlo and Polarizable Force Fields.Journal of chemical theory and computation · 2024Article
- Accelerated Enveloping Distribution Sampling to Probe the Presence of Water Molecules.Journal of chemical theory and computation · 2023Article
- WaterKit: Thermodynamic Profiling of Protein Hydration Sites.Journal of chemical theory and computation · 2023Article
- Enhanced Grand Canonical Sampling of Occluded Water Sites Using Nonequilibrium Candidate Monte Carlo.Journal of chemical theory and computation · 2023Article
- Molecular Modelling of Ionic Liquids: Situations When Charge Scaling Seems Insufficient.Molecules (Basel, Switzerland) · 2023Article
- Water Networks in Complexes between Proteins and FDA-Approved Drugs.Journal of chemical information and modeling · 2023Article
- Absolute Binding Free Energy Calculations for Buried Water Molecules.Journal of chemical theory and computation · 2022Article
- Large-Scale Ligand Perturbations of the Protein Conformational Landscape Reveal State-Specific Interaction Hotspots.Journal of medicinal chemistry · 2022Article
- An overview of the SAMPL8 host-guest binding challenge.Journal of computer-aided molecular design · 2022Article
- Enhancing sampling of water rehydration upon ligand binding using variants of grand canonical Monte Carlo.Journal of computer-aided molecular design · 2022Article
- Spatially Resolved Hydration Thermodynamics in Biomolecular Systems.The journal of physical chemistry. B · 2022Review
- Enhancing Sampling of Water Rehydration on Ligand Binding: A Comparison of Techniques.Journal of chemical theory and computation · 2022Article
- Fast Equilibration of Water between Buried Sites and the Bulk by Molecular Dynamics with Parallel Monte Carlo Water Moves on Graphical Processing Units.Journal of chemical theory and computation · 2021Article
- Automation of absolute protein-ligand binding free energy calculations for docking refinement and compound evaluation.Scientific reports · 2021Article
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Authors and funding
6 authors.
Funding
Abstract
Water molecules can be found interacting with the surface and within cavities in proteins. However, water exchange between bulk and buried hydration sites can be slow compared to simulation timescales, thus leading to the inefficient sampling of the locations of water. This can pose problems for free energy calculations for computer-aided drug design. Here, we apply a hybrid method that combines nonequilibrium candidate Monte Carlo (NCMC) simulations and molecular dynamics (MD) to enhance sampling of water in specific areas of a system, such as the binding site of a protein. Our approach uses NCMC to gradually remove interactions between a selected water molecule and its environment, then translates the water to a new region, before turning the interactions back on. This approach of gradual removal of interactions, followed by a move and then reintroduction of interactions, allows the environment to relax in response to the proposed water translation, improving acceptance of moves and thereby accelerating water exchange and sampling. We validate this approach on several test systems including the ligand-bound MUP-1 and HSP90 proteins with buried crystallographic waters removed. We show that our BLUES (NCMC/MD) method enhances water sampling relative to normal MD when applied to these systems. Thus, this approach provides a strategy to improve water sampling in molecular simulations which may be useful in practical applications in drug discovery and biomolecular design.
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